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Introduction: Glycoprotein B (gB) is the major antigen for induction of humoral responses against human cytomegalovirus (HCMV) making it an attractive candidate for immune prophylaxis. In the present study, the humoral immune response of BALB/c mice to a truncated HCMV gB protein fused with GFP was evaluated. Methods: The truncated gB coding sequence was synthesized and cloned in pEGFPN1 eukaryotic expression vector and expressed in HEK 293T cell line. After optimization, expression of the recombinant truncated HCMV gB was verified using HRP-conjugated polyclonal antibody specific for HCMV gB.The level of humoral immune responses was assessed in mice using DNA/DNA, peptide/peptide, and DNA/ peptide (prime-boost) immunization strategies. Results: Cloning of the truncated gB coding sequence in the pEGFPN1 was verified by restriction enzyme analysis and sequencing. After optimizing the transfection procedure the number of the GFP positive cells reached 32%. Western blot analysis confirmed the in vitro expression of the truncated HCMV gB protein with an apparent molecular weight of approximately 70 kDa. In vivo prime-boost immunization using HCMV gB DNA/peptide regimen showed significantly higher humoral immune responses compared to the control groups. Conclusion: This study demonstrated that the pEGFPN1 eukaryotic expression vector could be used to optimize and evaluate the expression of this truncated protein.The results also showed that the DNA/peptide vaccination could induce a significant antibody response in animal model.

Herpes simplex virus type 1 (HSV-1) is responsible for a wide range of human infections, including skin and mucosal ulcers, encephalitis, and keratitis. The gold standard for treating HSV-1 infections is acyclovir. However, the use of this drug is associated with several limitations such as toxic reactions and the development of drug-resistant strains. So, there is an urgent need to discover and develop novel and effective agents against this virus. For the first time, this study aimed to investigate the antiviral effects of the Thermally Expanded Graphite (TEG)-copper oxide (CuO) nanocomposite against HSV-1 and compare results with its constituent components. After microwave (MW)-assisted synthesis of TEG and CuO nanosheets as well as MW-CuO/TEG nanocomposite and characterization of all these nanomaterials, an MTT assay was used to determine their cytotoxicity. The quantitative real-time PCR was then used to investigate the effects of these nanomaterials on viral load. Three-hour incubation of HSV-1 with TEG nanosheets (500 μg/mL), MW-CuO nanosheets (15 μg/mL), and MW-CuO/TEG nanocomposite (35 μg/mL) resulted in a decrease in viral load with an inhibition rate of 31.4 %, 49.2 %, and 74.4 %, respectively. The results from the post-treatment assay also showed that TEG nanosheets (600 μg/mL), MW-CuO nanosheets (15 μg/mL), and MW-CuO/TEG nanocomposite (10 μg/mL) led to a remarkable decrease in viral load with an inhibition rate of 56.9 %, 63 %, and 99.9 %, respectively. The combination of TEG and MW-CuO nanosheets together and the formation of a nanocomposite structure display strong synergy in their ability to inhibit HSV-1 infection. MW-CuO/TEG nanocomposites can be considered a suitable candidate for the treatment of HSV-1 infection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ahmad Tavakoli reports financial support was provided by Iran University of Medical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: To determine the epidemiology of rotavirus group A (RVA) infection in symptomatic children, and analyze genotype diversity in association with clinical characteristics, geographical and seasonal changes., Methods: The stool samples of symptomatic children 5≥ years old were collected from 5 different hospitals during December 2020 and March 2022. Rotavirus stool antigen test was done and G and P genotypes of the positive samples were determined. Associations of the infection and genotype diversity with demographical and clinical data were assessed by statistical methods., Results: RVA infection was detected in 32.1% (300/934) of the patients (Ranges between 28.4% and 47.4%). An inverse association with age was detected, where the highest frequency was measured in children ≤12 months of age (175/482, 36.3%). The infection was more frequent during winter (124/284, 43.7%) and spring (64/187, 34.2%). Children who were exclusively fed with breast milk showed a lower rate of infection (72/251, 28.6%). Among the 46 characterized genotypes (17 single- and 29 mixed-genotype infections), G1P[8] and G9P[4] were more frequently detected in children <36 (67/234, 28.63%) and 36-60 (7/24, 29.16%) months of age children, respectively. A seasonal diversity in the circulating genotypes was detected in different cities. Children with G1P[8], G1P[6], and mixed-genotype infection experienced a shorter duration of hospitalization, and a higher frequency of nausea and severe diarrhea, respectively., Conclusions: In this study high frequency of RVA infection was detected in symptomatic children in Iran. Moreover, genotype diversity according to geographic area, seasons, age groups, and clinical features of disease was detected., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Group A rotaviruses are the most common cause of gastroenteritis in children under five years of age worldwide. Rotavirus gastroenteritis can be related to mild to severe diarrhea in children and in some cases, can lead to death due to severe dehydration. Approximately 146,480 people die annually from rotavirus infection worldwide, and most of these deaths occur in low-income countries in Africa and Asia. Since there are no specific effective drugs to treat rotavirus infections, and infected patients can only be treated supportively, new antiviral agents need to be developed. Copper oxide nanoparticles (CuO NPs) have a wide range of applications in the magnetic and electrical industries, as well as in biology. The antiviral activity of nanoparticles (CuO NPs) is well documented. This study aimed to investigate the antiviral effect of CuO NPs on rotaviruses. The cytotoxic effects of CuO NPs on MA-104 cells were examined by methyl thiazolyl tetrazolium assay. In addition, the anti-rotavirus activity of CuO NPs was evaluated by TCID 50 and real-time polymerase chain reaction PCR assay. Our results showed that exposure of rotavirus-infected cells to various non-toxic concentrations of CuO NPs did not cause a decrease in viral titer, compared to the control. However, the virucidal effect of CuO NPs on rotavirus was observed at concentrations of 80 and 100 μg/ml ( P <0.001). Our study suggested that CuO NPs had significant antiviral activity against rotavirus replication. However, the exact mechanism of anti-rotavirus activity of CuO NPs remained unknown. According to the virucidal assay, it appears that the loss of capsid integrity and genome disruption in the presence of CuO NPs are possible mechanisms of its anti-rotavirus activity., Competing Interests: The authors declare that they have no conflict of interest.

Background: Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist., Objective: In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years., Methods: In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques., Results: The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35&#95;AD., Conclusion: Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Since the emergence of the original Wuhan SARS-CoV-2 strain, several new variants of the virus have emerged. Alpha, Beta, Gamma, Delta and the most recent Omicron variants have been introduced during this pandemic. Several methods including, but not restricted to, allele-specific PCR, ligation with rolling circle amplification and real-time PCR with allele-specific probes are able to detect mutations as low as a single nucleotide polymorphism. High-resolution melting curve analysis is ano-ther technique to assess any mutations in a nucleic acid chain. Confirmed samples with SARS-CoV-2 infection were subjected to variant identification using a de novo-designed HRM assay. In order to select for mutations with the highest effect on Tm of the amplicon, deletion mutations of NSP6 (Del 3675-3677), and S1 (Del 144) were chosen for HRM analysis. HRM analysis for the amplicon of the primer set-1 (NSP6) resulted in Tm differences of -0.39°C, +0.4°C, and -0.6°C between Alpha, Delta, and Omicron variants, respectively, in comparison to the original Wuhan strain. Moreover, HRM analysis of the amplification performed by primer set-2 (S1) led to Tm differences of +0.32°C, -0.26°C, and +0.24°C between Alpha, Delta, and Omicron variants, respectively, in comparison to original Wuhan strain. The test was able to specify each sample to its variant group with more than 90 percent of confidence. The results obtained in this study demonstrate that using a single closed-tube strategy with a HRM-equipped machine, screening new variants of the virus is possible in a fast and reliable way. Keywords: high resolution melting; SARS coronavirus 2; mutation; variant; genotyping.

Background: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication., Objective: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection., Methods: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID 50 , and real-time PCR assays., Results: The highest inhibitory effect was obtained at concentrations of 0.5 μg/ml of amlodipine and 3 μg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the C t values compared to the virus control, respectively ( p -value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 μg/ml of amlodipine and above 25 μg/ml of diltiazem., Conclusion: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Glioblastoma multiforme (GBM) is an aggressive form of adult brain tumor that can arise from a low-grade astrocytoma. In recent decades, several new conventional therapies have been developed that have significantly improved the prognosis of patients with GBM. Nevertheless, most patients have a limited long-term response to these treatments and survive < 1 year. Therefore, innovative anti-cancer drugs that can be rapidly approved for patient use are urgently needed. One way to achieve accelerated approval is drug repositioning, extending the use of existing drugs for new therapeutic purposes, as it takes less time to validate their biological activity as well as their safety in preclinical models. In this review, a comprehensive analysis of the literature search was performed to list drugs with antiviral, antiparasitic, and antidepressant properties that may be effective in GBM and their putative anti-tumor mechanisms in GBM cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Coronary artery disease (CAD) is a leading cause of death around the world. Micro-ribonucleic acid (miRNA) can be involved in forming of atherosclerotic plaques, inflammation, cholesterol metabolism, and other mechanisms involved in CAD development. This study aimed to evaluate the expression level of miR-22, miR-30c, miR-145, and miR-519d and their possible association with inflammatory markers among patients with CAD., Methods: The expression level of miR-22, miR-30c, miR-145, miR-519d, interleukin 6 (IL-6), and transforming growth factor beta (TGF-β) was determined in peripheral blood mononuclear cells (PBMCs) from 46 patients with CAD and 39 healthy controls using real-time quantitative polymerase chain reaction (qPCR) assay., Results: 53.8% (n = 21) and 52.2% (n = 24) of controls and cases were men, respectively; the mean age was 59.8 ± 7.4 and 57.0 ± 9.8 years, respectively. The miRNA expression pattern of each group showed significantly different expression profiles. In the CAD patients group, miR-22, miR-30c, and miR-145 were down-regulated compared to the control group. On the opposite, miR-519d was up-regulated in patients with CAD compared to the control group. Our results also showed that the expression levels of IL-6 and TGF-β were up-regulated among patients with CAD compared to the control group. In addition, the expression of miR-145 and miR-519d had a significantly negative and positive correlation with TGF-β and IL-6, respectively., Conclusion: The change in expression levels of miR-22, miR-30c, miR-145, and miR-519d in PBMCs of patients with CAD could be considered as a potential biomarker for CAD., (© 2022 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.)

Background: Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear., Objective: The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs., Methods: MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed., Results: The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression., Conclusion: The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in patients with glioblastoma multiforme (GBM)., Methods: This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively., Results: HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001)., Conclusion: Our findings indicate that infection with EBV is associated with GBM.

Men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviours. In this study, a meta-analytic approach was used to systematically analyse the literature to elucidate the prevalence and genotype distribution of anal, penile, oral and urethral HPV infection among MSM in the world. To carry out this systematic review, five electronic databases including Web of Science, PubMed, Scopus, Embase, and Google Scholar were searched for relevant studies published from January 2012 to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalence was calculated for each anatomical region using a random-effect model weighted by the inverse variance method. The meta-analysis was performed using the "Metaprop" function in the R package Meta. The overall pooled prevalence of anal, penile, oral and urethral HPV infection among MSM were 78.4% (95% confidence interval [CI]: 75.6%-81.0%), 36.2% (95% CI: 29.1%-44.0%), 17.3% (95% CI: 13.6%-21.7%) and 15.4% (95% CI: 7.8%-27.9%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis and oral cavity was HPV-16 (19.9%, 4.9% and 3.1%, respectively). HPV infection is rising in MSM because of high-risk sexual behaviours, suggesting an increased future risk of developing HPV-related diseases and malignancies in this population., (© 2021 John Wiley & Sons Ltd.)

Background: Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not associated with significant disease in general population, while people with underlying problems such as immunodeficiency can cause anemia and arthritis. The current systematic review and meta-analysis aimed to estimate the overall prevalence of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies in blood donors worldwide., Methods: A systematic search was carried out in online databases for relevant studies from inception until March 30, 2019. Study selection was performed based on predesigned eligibility criteria. The proportion of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies were pooled using the inverse variance method. All statistical analyses were performed using the R version 3.5.3, package "meta.", Results: According to the random-effects model, the pool prevalence of B19V DNA, anti-B19V IgM, and anti-B19V IgG among blood donors was calculated to be 0.4% (95% confidence interval [CI] =0.3%-0.6%), 2.2% (95% CI = 1.3%-3.7%), and 50.1% (95% CI = 43.1%-57.1%), respectively., Conclusion: For the transmission of B19V through blood, the presence of the virus genome is required, and the present study showed that the prevalence of the virus genome in blood donors is <1%. Therefore, there is no need to screen donated blood for B19V infection., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Asian Journal of Transfusion Science.)

Background and Objectives: Helicobacter pylori causes several gastrointestinal diseases, including asymptomatic gastritis, chronic peptic ulcer, duodenal ulcer, lymphoma of the mucosa-associated lymphoid tissue (MALT), and gastric adenocarcinoma. In recent years, failure to eradicate H. pylori infections has become an alarming problem for physicians. It is now clear that the current treatment strategies may become ineffective, necessitating the development of innovative antimicrobial compounds as alternative treatments., Materials and Methods: In this experimental study, a cell-penetrating peptide-conjugated peptide nucleic acid (CPP-PNA) was used to target the cagA expression. cagA expression was evaluated using RT-qPCR assay after treatment by the CPPPNA in cell culture and animal model. Additionally, immunogenicity and toxicity of the CPP-PNA were assessed in both cell culture and animal models., Results: Our analysis showed that cagA mRNA levels reduced in H. pylori -infected HT29 cells after treatment with CPPPNA in a dose-dependent manner. Also, cagA expression in bacterial RNA extracted from stomach tissue of mice treated with PNA was reduced compared to that of untreated mice. The expression of inflammatory cytokines also decreased in cells and tissue of H. pylori -infected mice after PNA treatment. The tested CPP-PNA showed no significant adverse effects on cell proliferation of cultured cells and no detectable toxicity and immunogenicity were observed in mice., Conclusion: These results suggest the effectiveness of CPP-PNA in targeting CagA for various research and therapeutic purposes, offering a potential antisense therapy against H. pylori infections., (Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences.)

Background and Objectives: The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in breast cancer pathology is not well understood. Our study aimed to investigate the association of HCMV and EBV infections with breast cancer and distinguish the types of positive EBV and LMP-1 samples in Iranian patients., Methods: Seventy-two formalin-fixed paraffin-embedded (FFPE) breast cancer tissues were analyzed between December 2014 and April 2016. Samples were analyzed for HCMV and EBV using nested-PCR and conventional PCR assays, respectively. Statistical analysis was performed using SPSS software version 18., Results: Overall, HCMV and EBV genomes were detected in 6.9% and 16.7% of FFPE breast cancer tissues, respectively. Clinical factors were not statistically associated with the presence of HCMV and EBV., Conclusion: In this study, we reported EBV and LMP-1 typing in breast carcinoma cases for the first time in Iran. Our findings indicate that HCMV and EBV infections are not associated with the development of breast cancer.

Background: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are important public health issues., Objective: This study aimed to assess the association between microRNAs expression leveland immunological and viral markers in HIV, HCV, and HIV/HCV co-infected patients., Methods: The expression level of miR-29, miR-149, miR-199, miR-let7, miR-223, miR-155, miR-122, and miR-150 was evaluated in 20 HIV, 20 HCV, 20 co-infected patients, and 20 healthy controls using real-time PCR assay. HIV and HCVviral loads were measuredby real-time PCR, and also, CD4+ T-lymphocyte count was measuredby the PIMA CD4 analyzer., Results: The miRNA expression pattern in each mentioned group showed significantly different expression profiles, but some miRNA species were shared between the groups. MiR-122 and miR-155 were upregulated, while miR-29 and miR-223 were downregulated in three patients groups compared to healthy controls. A significant positive correlation was observed between the expression of miR-122 and HIV/HCV loads. But, miR-29 and let-7 were negatively correlated with HIV load, and miR-149 and let-7 were negatively correlated with HCV load. Also, miR-155 was positively correlated with HCV load. MiR-122 and miR-199 were negative while others were positively correlated with CD4+ T cell count., Conclusion: These miRNAs are probably involved in the clinical progression and pathogenesis of HIV and HCV infections. Therefore, determining and manipulating these miRNAs can lead to opening a new gate to control these important infections., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Female sex workers (FSWs) are amongst the most susceptible groups to acquire human papillomavirus (HPV) infection and consequently, to develop cervical intraepithelial neoplasia and cervical cancer. This is the first systematic review and meta-analysis to provide estimates of the pooled prevalence of HPV infection and the distribution of HPV types among FSWs across the world., Methods: Five computerized databases were searched for relevant studies published since the inception date of databases to September 2019. The pooled HPV prevalence was calculated by the random effect model described by DerSimonian-Laird. Subgroup analysis was performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the "Metaprop" function in the R package Meta., Results: Sixty-two studies involving 21,402 FSWs from 33 countries were included in this meta-analysis, and the pooled HPV prevalence was 42.6% (95% confidence interval (CI): 38.5-46.7%). HPV-16 (10.1, 95% CI: 8.2-12.5%), HPV-52 (7.9, 95% CI: 5.9-10.7%), and HPV-53 (6.0, 95% CI: 4.4-8.1%) were the most common high-risk HPV types identified among FSWs. The pooled estimated prevalence of HPV infection among FSWs before and after 2010 were slightly different, 43.6% (95% CI: 36.1-51.4%) and 41.9% (95% CI: 37.2-46.8%), respectively., Conclusion: Due to the high prevalence of HPV infection, particularly with high-risk types, FSWs have a great susceptibility to the development of cervical and vaginal cancers. Furthermore, they can transmit their infection to their clients, which may result in a high prevalence of HPV and the incidence of HPV-associated malignancies among the general population.

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc , promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1 , more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P  = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC., Competing Interests: Competing interestsAll the authors have stated to have no conflict of interest for declaration., (© The Author(s) 2020.)

Background: Numerous studies conducted over the past 30 years have pointed to the presence of Epstein-Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer., Methods: A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a random-effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies. Two separate analyses were performed on data from case-control studies with matched and non-match pairs designs to calculate the pooled estimates of ORs., Results: The pooled prevalence of EBV in 20,361 gastric cancer patients was 8.77% (95% CI: 7.73-9.92%; I 2  = 83.2%). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled ORs were 18.56 (95% CI: 15.68-21.97; I 2  = 55.4%) for studies with matched pairs design and 3.31 (95% CI: 0.95-11.54; I 2  = 55.0%) for studies with non-matched pairs design. The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.83%, vs. 5.72%) (P < 0.0001). However, the pooled OR estimate for EBV-associated gastric cancer was significantly higher among females (21.47; 95% CI: 15.55-29.63; I 2  = 0%) than in males (14.07; 95% CI: 10.46-18.93; I 2  = 49.0%) (P = 0.06). EBV was more prevalent in the cardia (12.47%) and the body (11.68%) compared to the antrum (6.29%) (P = 0.0002)., Conclusions: EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer. Our findings showed that using tumor-adjacent normal tissues as the control group provides more robust and accurate results regarding the relationship between EBV infection and gastric cancer.

The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35&#95;AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.

Although an increasing number of studies have been conducted to evaluate the association between human papillomavirus (HPV) infections and distribution of HPV types worldwide with the risk of prostate cancer (PC), the results remain inadequate. Hence, we investigated the association between HPV infection and PC risk using a meta-analysis. Relevant studies from January 1990 to December 2016 were searched in PubMed, Web of sciences, and Scopus databases. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to find the association between the prevalence of HPV and prostate cancer risk. To do so, data from 24 studies with 5546 prostate cancer cases were pooled in order to evaluate the heterogeneity of chief parameters including study region, specimen type, HPV DNA source, detection technique, publication calendar period, and Gleason score. All statistical analyses were performed using STATA 11 and MedCalc 13. A significant positive association was found between HPV infection and PC risk (OR = 1.281; P = 0.026). The genotype 16 was more frequently found in patients with PC which significantly increased the cancer risk (OR = 1.60; P < 0.001). Age 65 and older could significantly escalate PC risk (OR = 3.564; P < 0.001). Our results clearly favor the potential pathogenetic link between HPV infection and increased risk of PC affirming that HPV infections could play a part in the risk of PC., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 influenza virus., Methods: The nanoparticles were characterized using the inductively coupled plasma mass spectrometry, x-ray diffraction analysis, and electron microscopy. MTT assay was applied to assess the cytotoxicity of the nanoparticles, and anti-influenza activity was determined by TCID50 and quantitative Real-Time PCR assays. To study the inhibitory impact of nanoparticles on the expression of viral antigens, an indirect immunofluorescence assay was also performed., Results: Post-exposure of influenza virus with PEGylated ZnO-NPs and bare ZnO-NPs at the highest non-toxic concentrations could be led to 2.8 and 1.2 log10 TCID50 reduction in virus titer when compared to the virus control, respectively (P < 0.0001). At the highest non-toxic concentrations, the PEGylated and unPEGylated ZnO-NPs led to inhibition rates of 94.6 and 52.2%, respectively, which were calculated based on the viral loads. There was a substantial decrease in fluorescence emission intensity in viral-infected cell treated with PEGylated ZnO-NPs compared to the positive control., Conclusions: Taken together, our study indicated that PEGylated ZnO-NPs could be a novel, effective, and promising antiviral agent against H1N1 influenza virus infection, and future studies can be designed to explore the exact antiviral mechanism of these nanoparticles.

Retinoblastoma tumor (RB) is one of the most prevalent ocular cancers among children. RB may be caused by inherited mutations in RB1 gene as well as some environmental risk factors. Human papillomaviruses (HPV) are suspected as a risk factor of RB due to their pRb inactivating protein. This study evaluated the molecular prevalence of HPV among the RB tumor specimens in Iran. The RB tumor samples were tested for detection of HPV-L1 gene using a nested-PCR approach, and then followed by sequencing and phylogenetic analysis to reveal HPV types. Overall, there were 61 RB tumor samples; 54/61 (88.5%) had unilateral and 7/61 (11.5%) bilateral RB; 55/61 cases (90.2%) had sporadic non-familial RB tumor. HPV-DNA was detected in 6/61 (9.8%) of patients' tumors; the HPV positive RB cases all had unilateral and unfamiliar sporadic RB tumor. HPV type 16 was the most prevalent type identified across the RB tumor samples (3/61, 4.9%). The rate of detected HPV among the RB specimens seems to be considerable. Further investigations are required to elucidate the exact association between HPV and progression to RB., Competing Interests: Conflict of interestAll the authors have stated to have no conflict of interest to declare., (© Indian Virological Society 2019.)

Despite the numerous publications regarding the role of Epstein-Barr virus (EBV) in breast cancer development, the topic has still remained controversial. The aim of the meta-analysis was to estimate the overall prevalence of EBV in the breast cancer population, and to investigate the association between EBV and breast cancer risk. The overall prevalence of EBV was calculated 26.37% (95% CI: 22-31%) from the 44 included studies. Meta-analysis of 30 case-control studies showed that the pooled association between EBV and risk of breast cancer is odds ratio 4.74 (95% CI: 2.92-7.69; Z = 6.30; p < 0.0001). Our analyses indicate a strong statistical relationship between EBV infection and risk of breast cancer, suggesting a potential role of EBV infection in the development of breast cancer.

Background: Some studies implicate rotavirus infection as a trigger for the development of type 1 diabetes mellitus (T1DM) in children, however findings are controversial., Objectives: We investigated the link between rotavirus infection and autoantibodies against islet antigens and T1DM in children., Methods: Serum samples from 80 new-onset diabetic and 80 nondiabetic children were screened for anti-rotavirus IgG, anti-GAD65 and anti-IA-2 autoantibodies using ELISA kits., Results: Positivity percentages of anti-rotavirus IgG detection in diabetic and nondiabetic children were 51.3% and 35.0%, respectively (p = 0.03). The mean anti-GAD65 and anti-IA-2 antibody titers in anti-rotavirus IgG positive samples were statistically higher than that the anti-rotavirus IgG negative samples. A positive correlation was found between anti-rotavirus IgG and anti-GAD65 antibody levels (p = 0.004; r = 0.22)., Conclusions: Our findings support the hypothesis that rotovirus infection may induce T1DM in children.

Multiple Sclerosis (MS) is thought to be an autoimmune disease of the central nervous system (CNS), in which the immune system becomes activated, cross the blood-brain barrier (BBB), and cause neuroinflammation and neurodegeneration. Fingolimod is considered a disease-modifying therapy (DMT), possessing immunomodulatory effects on the immune system, especially autoreactive T cells being licensed in lymph nodes. Although the fidelity of the drug is undeniable in the management of disease course, various adverse effects have been reported in some patients taking this medication. In this study, 420 MS patients, consisted of 210 patients receiving interferon-beta (IFN-beta) and 210 patients receiving fingolimod therapies. As a control group, 210 age- and sex-matched healthy individuals were recruited in our study. The levels of anti-VZV IgG and IgM were determined using enzyme-linked immunosorbent assay (ELISA). The presence of VZV DNA in peripheral blood mononuclear cells (PBMCs) was also investigated using the PCR method. The percentage of seropositivity for anti-VZV IgG and anti-VZV IgM in MS patients was 94.8% and 0%, respectively in those taking fingolimod therapy. In patients receiving IFN-beta, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 93.8% and 0%, respectively. In healthy individuals, the rate of seropositivity for anti-VZV IgG and anti-VZV IgM was 84.3% and 0%, respectively. The PCR results showed that 7.6% of patients receiving fingolimod were positive for VZV DNA, while none of the healthy subjects nor MS patients taking IFN-beta were positive for DNA of VZV. The statistical analysis indicated that the frequency of VZV DNA in patients receiving fingolimod was significantly (p = .00) higher than MS patients taking IFN-beta and healthy subjects. It seems that the use of fingolimod should be carefully prescribed as the occurrence of VZV infection/reactivation is increased in comparison to other MS patients who receive different therapy., (Copyright © 2018. Published by Elsevier B.V.)

Occult HCV infection (OCI) has been described as the presence of hepatitis C virus (HCV) genomic RNA in hepatocytes and/or peripheral blood mononuclear cell (PBMC) specimens and the lack of HCV genomic RNA and anti-HCV antibodies (Abs) in plasma samples. Injection drug users (IDUs) are the most important high-risk group for infection with blood-borne viruses, particularly HCV. The purpose of this study was to determine the presence of OCI in IDUs. A prospective cross-sectional study of 126 consecutive Iranian IDUs was performed from March 2017 to January 2018. PBMCs were separated from blood samples from the participants, and after extraction of the viral RNA from the plasma and PBMC specimens, HCV RNA was detected in the samples using RT-nested PCR by amplification of the 5'-NTR of HCV. HCV genotyping was carried out using restriction a fragment length polymorphism (RFLP) assay. The viral RNA was amplified using RT-nested PCR with specific primers for the NS5B gene, and the PCR products were sequenced to confirm the results obtained by HCV RNA detection and HCV genotyping. Out of the 126 IDUs studied, 105 (83.3%) were negative for anti-HCV Abs and HCV RNA in plasma samples, whereas HCV RNA was detected in the PBMC samples of six (5.7%) participants, indicating that these individuals had OCI. Moreover, HCV genomic RNA was detected in PBMC samples from five (23.8%) of the 21 IDUs studied who were positive for anti-HCV Abs and negative for HCV genomic RNA in plasma specimens. These IDUs also had OCI. The HCV genotypes in the PBMC samples from the subjects with OCI were determined. Six (54.5%) subjects were infected with HCV subtype 3a, and five (45.5%) were infected with HCV subtype 1a. This study showed that 8.7% of the Iranian IDUs had OCI, and therefore, a study focusing on the diagnosis of OCI in these individuals can be valuable and informative.

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs., Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated., Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database., Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35&#95;AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children., Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Different outcomes of parvovirus B19 (B19V) infection in immunocompromised patients, including HIV1-infected persons, may be life-threatening. Considering the hematologic disorders associated with B19V infection, this study aimed to investigate the prevalence of B19V infection among HIV1-infected individuals in Iran. Methods: Serum samples from 100 HIV1-infected patients were analyzed for B19 viral DNA using real-time PCR assay. COBAS TaqMan HIV-1 test was performed for quantitative measurements of HIV-1 RNA in the patients' sera. Results: Real-time PCR analysis revealed that 10 out of 100 cases (10%) were positive for B19V infection. Across various age groups, the B19V infection was more prevalent among patients within the age range of 21-40 years. Higher prevalence of B19V infection was observed among HIV1-infected patients with a viral load of higher than 400 copies/mL. Conclusion: Despite limitations, this study may set the stage for further evaluations with larger sample sizes to elucidate the potential role of B19V in hematologic disorders, which may result in exacerbation of the disease in HIV1-infected patients. Moreover, as it has been shown that B19V infection can be treated using intravenous immunoglobulin (IVIG) therapy, available treatments may help improve the quality of life in HIV-infected persons.

Aim: We aimed to determine the possible inhibitory effects of zinc oxide nanoparticles (ZnO-NPs) and polyethylene glycol (PEG)-coated ZnO-NPs (ZnO-PEG-NPs) on herpes simplex virus type 1 (HSV-1)., Materials & Methods: PEGylated ZnO-NPs were synthesized by the mechanical method. Antiviral activity was assessed by 50% tissue culture infectious dose (TCID 50 ) and real-time PCR assays. To confirm the antiviral activity of ZnO-NPs on expression of HSV-1 antigens, indirect immunofluorescence assay was also conducted., Results: 200 μg/ml ZnO-PEG-NPs could result in 2.5 log 10 TCID 50 reduction in virus titer, with inhibition rate of approximately 92% in copy number of HSV-1 genomic DNA., Conclusion: ZnO-PEG-NPs could be proposed as a new agent for efficient HSV-1 inhibition. Our results indicated that PEGylation is effective in reducing cytotoxicity and increasing antiviral activity of nanoparticles.

Due to the similar routes of transmission, individuals infected with the human immunodeficiency virus (HIV) may become infected with the hepatitis C virus (HCV) simultaneously. The aim of this study was to investigate the frequency of HCV co-infection in Iranian individuals with HIV infection, and to genotype HCV in plasma and PBMC specimens of these patients. From September 2015 to October 2016, a total of 140 Iranian individuals with HIV infection were enrolled in this cross-sectional study. The RNA from plasma and PBMC specimens was extracted, and genomic HCV-RNA was amplified using RT-nested PCR with primers that target 5'-UTR. The HCV genotyping used the RFLP technique. To confirm HCV genotype, 10 randomly selected HCV-positive samples were also submitted for sequencing. The mean age of patients was 35.7 ± 13.5 years (range: 1-66). Out of 140 patients, 62 (44.3 %) were positive for anti-HCV antibodies; among these, viral genomic RNA was detected in 34 (24.3%) and 39 (27.9%) of the plasma and PBMC specimens, respectively. The HCV genotyping showed a similar pattern of subtypes 1a (44% vs 46.2%), 3a (32.4% vs 33.3%), and 1b (17.6% vs 17.9%) in all sera and PBMC samples. It is noteworthy that the HCV genotypes in plasma and PBMC specimens of 6 HCV co-infected patients were not the same. This study reveals that HIV/HCV co-infection is high in Iranian patients (44.3%), especially in people who have high-risk factors (83.9%). Also, HIV/HCV co-infected individuals may have dissimilar HCV genotypes in their plasma and PBMC specimens., (© 2017 Wiley Periodicals, Inc.)

Background: Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus, which has been detected in patients with prostate cancer, chronic fatigue syndrome, and general population with a number of acquired infections such as infection with human T-cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV). The aim of this study was to determine the HTLV-1 and XMRV coinfection for the first time in Iranian patients who were admitted to the Tehran hospitals., Materials and Methods: Two hundred and ninety one patients suspected with HTLV-1 were referred to the hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran from April 2012 to October 2016. Genomic deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from peripheral blood mononuclear cells/cerebrospinal fluids was extracted by High Pure Viral Nucleic Acid Kit (Roche, Germany). After complementary DNA synthesis, conventional reverse transcriptase polymerase chain reaction was used for the detection of HTLV-1 or XMRV-infected patients. Statistical Package for Social Sciences (SPSS) software, version 16 (SPSS, Chicago, IL, USA) was used for statistical analyses., Results: Of the 291 patients suspected of HTLV infection, 123 (42.3%) were male with a mean age of 38±15 years. HTLV-1 RNA was found in 93 (31.9%) specimens comprising 40 men (41.3%) and 53 women (56.9%). Of the 93 patients who were HTLV-1 positive, one sample (1%) was positive for XMRV env gene., Conclusion: These findings suggest that the lack of significant detection of XMRV in patients who were HTLV-1 positive could not be associated with complications of HTLV-1. Although this is a preliminary report from Iranian patients with HTLV-1, further studies are needed to show the actual prevalence of XMRV infection by geographical distribution and various populations., Competing Interests: There are no conflicts of interest.

The presence of hepatitis B virus (HBV) DNA in the absence of traceable hepatitis B surface antigen (HBsAg) in the plasma specimen of patients is defined as occult HBV infection (OBI). This study aimed to detect HBV-DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of Iranian HBsAg negative patients with human immunodeficiency virus (HIV) infection. This cross-sectional study was conducted on 172 patients with HIV infection from September 2015 to August 2017. The patients were tested for serological parameters (HBsAg, HBcAb, HBeAg and HBeAb) against HBV infection. Moreover, they were tested for HBV viral load (using COBAS TaqMan 48 Kit, Roche, USA) in plasma and the presence of the HBV genome in PBMC specimens using real-time PCR. The mean age of the patients was 35.4 ± 13.4 years. Of the 172 studied patients, 109 (63.4%) were male. In this study, 151 (87.8%) patients were negative for HBsAg, 111 (64.5%) patients were negative for all HBV infection serological markers, 9 (5.2%) patients were only positive for HBsAg and 29 (16.9%) patients were only positive for HBcAb. Moreover, five (3.3%) patients with HBsAg negative had OBI (in the plasma sample of four patients and PBMC specimens of all five patients, HBV-DNA was detected). The present study revealed that 3.3% of the patients with HIV infection had occult HBV infection. Presumably, designing prospective studies to identify this infection in patients with HIV infection is informative and valuable.

Background: Respiratory infections, especially viral infections, are the most prevalent infection affecting Hajj pilgrims. Commonly major human influenza viruses (A/H1N1, A/H3N2, and B) are responsible for these morbidities. The present study was conducted to develop a statistical report on human influenza in Hajj pilgrims. Methods: Nasal and throat samples were collected from 232 returning Iranian pilgrims in hospitals of IUMS. All samples were kept in the refrigerator at 4 °C and stored at -70 °C until RNA extraction. RNA extraction was performed by QIAamp viral RNAmini kits (QIAGEN, Hilden, Germany) and influenza viruses were detected by TaqMan RT-PCR. Results: Participants included 115 (49.5%) male and 117 (50.5%) female patients, with the age range of 10 to 93 years (mean: 53 years). The pandemic and seasonal influenza A (H1N1) virus were detected in 2 (0.8%) and 20 (8.6%) pilgrims, respectively, and also influenza B was identified in 1 person (0.4%). Conclusions: Since the probability of an influenza pandemic has been anticipated for the coming years, it seems necessary to plan a continuous monitoring of large gatherings like Hajj and conduct statistical studies in the region. Moreover, material surveillance in humans needs to be boosted. Therefore, results of influenza research can be important for developing WHO reports.

Background: Human parvovirus B19 was known as one of the possible cause of mild respiratory tract diseases in previous studies. However, there are some reports of acute obstructive respiratory disease and severe pneumonia. The purpose of current study was to assess the prevalence and clinical features of parvovirus B19 in respiratory infection. Methods: This study was conducted on 156 patients diagnosed with respiratory infection at the Iran University of Medical Sciencesaffiliated hospitals. After extraction of viral DNA from swab samples, detection of parvovirus B19 was performed by real-time PCR assay. Results: In 156 patient's samples, parvovirus B19 was found in 8 (5.1 %) cases including 5 males (5.9%) and 3 females (4.1%). The most common clinical symptoms were wheezing (100%), tachypnea (100%), fever (75%) and rhinorrhea/pharyngitis (75%). Conclusion: This is the first attempt to assess the prevalence of parvovirus B19 infection in Iranian patients with respiratory infection. The low frequency of parvovirus B19 detected in our study does not support the role of this virus in the development of respiratory infection. However, further studies are needed to better evaluate the etiological role of parvovirus B19 in respiratory infection.

Human immunodeficiency virus (HIV) infection is mostly spreading in developing countries. One of the most important pathways of HIV infection in these nations is the vertical route, from mother to infant. Therefore, this study evaluated the effectiveness of the prevention of mother-to-child transmission (PMTCT) program for HIV among Iranian neonates born to HIV-positive mothers. A total of 54 neonates born to HIV-1 positive mothers, all of whom were in a PMTCT program for HIV, as per the Iranian guidelines, were enrolled in this descriptive cross sectional study from March 2014 to July 2017. After RNA extraction of a plasma specimen, HIV-1 viral load was tested by an Artus HIV-1 RG RT-PCR Kit. Out of 54 evaluated neonates, 32 (59.3%) were male. The mean age of the HIV-infected mothers was 30.1 ± 5.4 (range: 19-47) years, and 36 (66.7%) of the mothers were in the age group 26-34 years. In the present study, it was found that none of the neonates whose mothers had previously entered PMTCT programs had HIV. 15 children were found who were born to HIV-positive mothers who had not entered the PMTCT program. Three of these children were infected with HIV (CRF35&#95;AD), and none of them carried HIV-1 variants with SDRMs. The results of this study indicate that if HIV-positive pregnant women enter the PMTCT program for HIV, they can realistically hope to give birth to a non-infected child.

Objective: This systematic review and meta-analysis was performed to determine the prevalence rate of influenza virus from different parts of Middle East region, and present an overall relative frequency (RF) for this region., Methods: The authors performed a systematic literature review from several reliable databases such as PubMed, ISI Web of Science and Scopus during 2000-2016. Furthermore, the keywords of this research were 'Influenza', 'Subtype', 'Seroprevalence', 'Incidence', 'Seroepidemiology', 'H1N1', 'H3N2', 'H5N1', 'H9N2', 'Middle-East' and 'Meta-analysis'. The reported data were selected according to inclusion and exclusion criteria., Results: The authors selected 71 studies out of 1147 for the present review. The overall estimation of the prevalence of influenza virus was 10.2% [95% confidence interval (CI): 10.1%-10.3%]. However, based on our records, the evident heterogeneity of influenza virus was observed among the studies (Cochran Q test, P value <.001 and I-squared = 100%). It should be noted that influenza virus infection's RF varied from 0.5% in Qatar to 70% in Syria., Conclusions: The results of this review are remarkable, they show that influenza infection RF is variable due to several factors. Thus, further researches should be taken to minimize the emergence and transmission of influenza virus., (© 2018 John Wiley & Sons Ltd.)

Background: The etiology and molecular mechanisms involved in the development of breast cancer still remain poorly understood. Some epidemiological studies have shown an association between human papillomavirus (HPV) and breast cancer. However, the findings are controversial., Objective: Our study was aimed to investigate the presence of HPV DNA in breast carcinomas of Iranian women., Methods: In total, 72 samples of formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer collected between December 2014 and April 2016 were examined. HPV DNA detection was performed by nested-PCR assay. Next, positive samples were subjected to genotyping by the CLART HPV2 microarray system. All statistical analysis was carried out using SPSS v.18.0., Results: HPV DNA was detected in 4/72 (5.55%) samples. Clinical factors were not statistically associated with HPV presence. However, CLART HPV2 microarray assay failed to determine the genotype of any positive samples., Conclusion: The low frequency of HPV detected in our study does not support an association between breast carcinoma and HPV infection. However, it is possible that HPV may be responsible for breast carcinogenesis only in small percentage of all breast cancer.

Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and shows great resistance to most disinfectants. Therefore, it is one of the common contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4) is a newly identified parvovirus, which is also prevalent in parenteral transmission. In this study, we aimed to evaluate the prevalence of B19V and PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran., Methods: This was a cross-sectional epidemiological study comprising nearly all people with hemophilia in this region. Whole blood samples were taken after patient registration and sent for plasma isolation. After nucleic acid extraction, B19V was detected with real-time polymerase chain reaction, PARV4 DNA was then detected using sensitive semi-nested PCR., Results: In total, there were 86 patients with hemophilia, with mean age 28.5±1.5 years. Of these, 90.7% were men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11 patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4 DNA. The prevalence of B19V was higher in middle-aged groups rather than younger people, whereas PARV4 infection was more common in younger patients ( P <0.05)., Conclusion: There was a high prevalence of B19V and PARV4 infection in this high-risk group of patients with hemophilia. Due to the clinical significance of the B19 virus, imposing more precautionary measures for serum and blood products is recommended., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal lung disease. One of the risk factors involved in the acquisition of IPF is viral infections, especially respiratory viruses. In the present study, we investigated the detection of respiratory viruses and the possible relationship between these viruses and IPF., Methods: This cross-sectional study was supported by the Iran University of Medical Sciences (IUMS), Tehran, Iran. A total of 40 respiratory samples (five nasopharyngeal and 35 bronchoalveolar lavage specimens) were obtained from IPF patients referred to IUMS hospitals between April 2015 and December 2016. Assays were performed using the CLART Pneumovir DNA array assay, which made it possible to detect five genera of respiratory viruses simultaneously.Results/Key findings. Altogether, 22 of the 40 participants were male. Respiratory syncytial virus (RSV), parainfluenza, rhino, corona and influenza viruses were found in 2.5 % (1/40), 7.5 % (3/40), 10 % (4/40), 2.5 % (1/40) and 0% (0/40) of cases, respectively., Conclusion: Determining a correlation between the viruses and IPF is not an easy task, and therefore, this will require more research. In addition, the CLART Pneumovir DNA array can be considered as a useful method for simultaneous detection of several viral respiratory infections.

Herpes simplex virus type 1 (HSV-1) causes serious infections particularly in immunocompromised patients. Methanolic extract of four plants were evaluated for their anti-viral effects against acyclovir resistant HSV-1 in HeLa cell line. The 50% cytotoxic concentration (CC50) as well as the effective minimal cytotoxic concentration of each plant extract were evaluated by MTT assay. Antiviral effects of the plant extracts on HSV-1 were examined at different concentrations of the extract. The effective minimal cytotoxic concentration was evaluated at different times of virus replication after infection. Virus titration was assessed by tissue culture infectious dose 50 (TCID50) method. Among the 4 plant extracts evaluated only Mentha pulegium L. extract was shown to exert the highest antiviral activity, with selectivity index (SI) 10.25. Direct treatment of HSV-1 with Mentha pulegium L. extract resulted in 1.7 log10 TCID50 reduction in virus titers after one hour. The highest reduction in HSV-1 infectivity was obtained 1 hour after the infection of the cells with virus resulting in 2.1 log10 TCID50 reduction as compared to the control. The antiviral effects of Mentha pulegium L. extract on HSV-1 after virus infection was more remarkable than the virucidal activity.

Interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) constitute important host-related factors influencing the response rate to Hepatitis C virus (HCV) standard antiviral therapy. In the last few years, several new technologies for SNP detection have been developed. However, the sensitivity and specificity of various methods are different and needs evaluation. Five different methods (resolution melting curve [RMC], polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP], PCR-sequencing analysis, amplification refractory mutation system [ARMS], and zip nucleic acid probe-based real-time PCR [ZNA]) were developed for genotyping rs12979860 associated with IL28B. In this study, limit of detection (LD), costs and turnaround time of these methods were compared in 350 subjects. As for IL28B rs12979860 polymorphisms, 348/350 (99.4%) samples were consistent among the five methods, while results for 2/350 (0.57%) samples were concordant by ZNAs and PCR-sequencing, and discordant by other methods. Without considering the cost of DNA extraction, the price of each reaction for ARMS-PCR, RMC, PCR-RFLP, ZNA and PCR-sequencing were respectively: US$3.10, US$5.0, US$5.50, US$8.50 and US$17.0. RMC was the fastest method, while the ZNA method was easy to use, reliable and effective. Lower LD was determined to be 50-60 copies/μL for the PCR-RFLP, RMC and ARMS-PCR assays; whilst ZNA assay was able to detect 2-3 copies/μL. In conclusion, in the current study, all four methods are suitable for IL28B rs12979860 genotyping, but the ZNA assay can be a reliable tool. Due to its lower LD for SNP identification, this method is better than others for detecting this type of polymorphism.

In recent years, the patterns of human immunodeficiency virus 1 (HIV-1) transmission in Iran have been changing gradually from drug injection to unprotected sexual contact. This study sought to investigate the phylogenetic trends and characteristics of transmitted drug resistance (TDR) mutations of HIV-1 in a population that is mainly infected through homo/heterosexual contacts. Sixty newly diagnosed antiretroviral-naive individuals with HIV infection living in Tehran were recruited to this survey, and among them, 42 subjects were established to be infected through sexual intercourse. Following amplification and sequencing of the main part of the HIV-1 pol region, phylogenetic and drug-resistance mutation (DRM) analysis was successfully performed on these 42 patients. Phylogenetic analysis showed that the majority of the subjects were infected with subtype CRF35&#95;AD (88%), followed by subtype B, with 7.1%, and subtype CRF01&#95;AE, with 4.7%. A total of 7.1% of the subjects were found to be infected with HIV-1 variants with surveillance drug-resistant mutations (SDRMs) according to the last world health organisation (WHO) algorithm. All of the identified SDRMs belonged to the non-nucleoside reverse transcriptase inhibitors (NNRTIs) class, including K103 N and V106A, which were found in three patients. Two minor HIV protease-inhibitor-related mutations (L10I and G73S) were detected in two patients, but these mutations are not included in the WHO SDRMs list. The dominance of HIV-1 subtype CRF35&#95;AD was observed among subjects of this study who were infected through sexual contact. The moderate prevalence of SDRMs (7.1%) in this population emphasises the fact that the risk of treatment failure in HIV-infected individuals might increase in the future, and preventive measures should be considered by health authorities.

The association of Merkel cell polyomavirus (MCP y V) with Merkel cell carcinoma (MCC) in immunocompromised individuals has been revealed in a number of surveys. The study of MCP y V specific antibody titers and viral loads in such patients has a great attraction for research groups interested in viral reactivation. In this cross-sectional study to evaluate MCP y V antibody titer, DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs), we examined 205 HIV-1 infected patients and 100 un-infected controls. The HIV-1 infected patients divided into two groups (HIV/AIDS and non-AIDS) according to their CD4 status. Total IgG antibody titer against MCP y V was analyzed by virus like particle (VLP)-based enzyme linked immunosorbent assay (ELISA). Presence of MCP y V-DNA in subject's PBMCs was examined by quantitative real-time PCR assay. Levels of anti-MCP y V IgG in HIV/AIDS patients were significantly higher than those in non-AIDS HIV-infected and control subjects (p value = <0.001). The prevalence rate of MCP y V-DNA in PBMCs of HIV/AIDS, non-AIDS HIV-infected and un-infected controls were 17%, 16%, and 14% respectively. The MCP y V viral load among the groups ranged between 0.15 to 2.9 copies/10 3 cells (median, 1.9 copies/10 3 cells), with no significant difference between the studied populations (p value = 0.3).

Background: Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran., Methods: This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay., Results: The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients., Conclusion: In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Aim of the Study: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which can be lethal with chronic complications. Viral infections may be associated with IPF and other fibrotic lung diseases. In the present study, we investigate for the first time in Iran the related viral etiology of IPF in order to detect three respiratory viruses; human adenovirus, enterovirus and bocavirus., Materials and Methods: In this cross-sectional study which was supported by Iran University of Medical Sciences, Tehran, Iran. The diagnostic criteria for IPF were based on internationally accepted clinical and imaging criteria in accordance with the 2011 IPF guidelines. 30 nasopharyngeal (NP) swabs or broncho-alveolar lavage (BAL) samples were obtained from the lung of IPF patients that were diagnosed by a sophisticated practitioner from April 2015 to February 2016. Real-time (RT) polymerase chain reaction (PCR) method was performed to detect the three viruses. Fluorescence dye of a labeled probe recorded the results in order to create positive and negative controls. SPSS version 20 software was used to calculate basic descriptive and frequency features., Results: Of 30 specimens, 13 (43.4%) were male and 17 (56.6%) were female with the total mean age ± standard deviation 68.2 ± 12.0. RT-PCR assay results illustrated there was no infection of human adenovirus, enterovirus, and bocavirus detected in these samples. Significant results between IPF incidence and variables were not significant (p > 0.05)., Conclusion: The causes of IPF in Iranian patients need more research although, based on the results of this study, there was no association between human adenovirus, enterovirus, bocavirus, and IPF., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study aims to determine the prevalence of herpes simplex virus (HSV) infection among pregnant women as well as congenital infection of their newborns in Tehran. One hundred samples of blood sera from pregnant women were analyzed for the presence of HSV specific antibodies. Umbilical cord blood samples from the newborns were analyzed for the presence of HSV DNA using real-time PCR. HSV IgG and IgM antibodies were found in 97% and 2% of pregnant women, respectively. Of all the 100 cord blood samples, 6 were positive for HSV DNA in which 2 cases were from mothers who had detectable IgM. It was notable that all corresponding mothers of six HSV positive infants had detectable IgG antibodies in their sera. It was demonstrated that the presence of HSV DNA in cord blood of newborns could be a risk marker for maternal-fetal transmission of the virus in asymptomatic pregnant women.

Background: Chronic hepatitis C virus (HCV) is associated with extra hepatic autoimmune disorders, while peg-IFNa-2a/RBV combination therapy may exacerbate these conditions. Autoantibodies to cytoplasmic structures, called rod and ring particles (RR), have strong associations with these patients and are identified by HEp-2 cells., Objectives: Our purpose was to study the correlation of autoantibodies to cytoplasmic rod and ring particles in the serum of patients with chronic HCV infection with their response to standard therapy., Methods: Serum samples were gathered from 120 patients with HCV infection (40 naive treatments, 40 with sustained virological response (SVR), and 40 with relapse response) during peg-IFNa-2a/RBV combination therapy and analyzed for the presence of RR antibodies by IIF on commercially available HEp-2 cell substrate slides from Euroimmun (Lu beck, Germany)., Results: Anti-rod and ring (anti-RR) autoantibodies were detected in only the serum of 1 out of 120 patients (0.8%), which belonged to a patient (out of 40) with relapse response (2.5%). No correlation was found between the types of response to peg-IFNa-2a/RBV combination therapy and the presence of anti-RR autoantibodies., Conclusions: The only HCV patient with RR autoantibodies previously had received IFN/ribavirin antiviral therapy. The presence of these autoantibodies is extremely rare in Iranian HCV patients. Further studies are warranted to determine the role of genetic background and geographical pattern in the prevalence of these novel autoantibodies worldwide., Competing Interests: Conflict of Interest:The authors of the present study declare no conflict(s) of interest.