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Objective To systematically review the reported cases of Creutzfeldt-Jakob disease (CJD) in Iran. Methods A comprehensive literature review of CJD cases in Iran was undertaken using the PubMed®, Scopus® and Google Scholar databases. In addition, the Iranian database MagIran was searched for Persian language reports. Case selection used the following criteria: (i) patients of Iranian origin; (ii) publication in peer-reviewed journals or reputable medical databases; (iii) a definitive diagnosis of CJD based on established diagnostic criteria. Results Thirteen cases from twelve reports were included in this systematic review. The majority of the cases were female (11 of 13; 84.6%). The mean ± SD age of patients at hospital admission was 59.38 ± 7.44 years. The findings of the case review suggested that the prevalence of CJD in Iran is not fully established. CJD may be misdiagnosed alongside other clinical signs. The most prevalent early indications of the disease were psychiatric and neurological in nature. A considerable delay in diagnosis was observed in some cases and there was a shortage of brain autopsy records. Conclusion Efforts to improve diagnostic capabilities, promote awareness and establish monitoring systems are necessary for managing the challenges of providing an early diagnosis of CJD in Iran.

The surveillance of wastewater treatment plant (WWTP) as the end point of SARS-CoV-2 shed from infected people arise a speculation on transmission of this virus of concern from WWTP in epidemic period. To this end, the present study was developed to comprehensively investigate the presence of SARS-CoV-2 in raw wastewater, effluent and air inhaled by workers and employee in the largest WWTP in Tehran for one-year study period. The monthly raw wastewater, effluent and air samples of WWTP were taken and the SARS-CoV-2 RNA were detected using QIAamp Viral RNA Mini Kit and real-time RT-PCR assay. According to results, the speculation on the presence of SARS-CoV-2 was proved in WWTP by detection this virus in raw wastewater. However, no SARS-CoV-2 was found in both effluent and air of WWTP; this presents the low or no infection for workers and employee in WWTP. Furthermore, further research are needed for detection the SARS-CoV-2 in solid and biomass produced from WWTP processes due to flaks formation, followed by sedimentation in order to better understand the wastewater-based epidemiology and preventive measurement for other epidemics probably encountered in the future.

Abstract Background Human papilloma virus (HPV) causes the most common sexually-transmitted infection especially among sexually-active individuals. The aim of study was to characterize the molecular characterization of HPV genotypes between 5176 female and male patients. Methods HPV DNA was extracted from genital swabs of the study participants and amplified by Real Time Polymerase Chain Reaction (PCR). Genotyping was performed for 2525 cases using REALQUALITY RQ-Multi HPV Detection Kit for the identification of 14 high risk (HR) and 2 low risk (LR) HPV genotypes. Demographic figures were analyzed in correlation with virological data statistically. Results Out of 5176 cases from 7 laboratories, 2727 (53%) were positive for HPV, of which. 2372(87%) women and 355 (13%) men were HPV positive. However, in an intra-gender analysis, positive rate was higher in men (355/637, 55.7%) than in women (2372/4539, 52%; P value 0.007). HPV positive patients were younger than negative individuals. Positive rate was higher among age categories 20–40. Genotyping was performed for 2525 cases. Out of 1219 (48%) patients who contained single genotypes, 566 (22%) and 653 (26%) harboured HR and LR genotypes, respectively. In females and males, 1189 (54%) and 117 (37%) contained multiple genotypes. No substantial associations were found between different age categories and HR/LR and multiple genotypes distribution. Conclusion The prevalence of HPV infection in both genders was high. However, men had a higher rate of infection. These observations highlighted the necessity for a plan for targeted education to younger population in the society as well as application of infection control measures against HPV infection, especially in terms of general population mass HPV vaccination.

A quantitative model on exposure to pathogenic viruses in air of recreational area and their corresponding health effects is necessary to provide mitigation actions in content of emergency response plans (ERP). Here, the health risk associated with exposure to two pathogenic viruses of concern: Rotavirus (RoV) and Norovirus (NoV) in air of water spray park were estimated using a quantitative microbial risk assessment (QMRA) model. To this end, real-time Reverse Transcriptase polymerase chain reaction (real-time RT-PCR) was employed to measure the concentration levels of RoV and NoV over a twelve-month period. The probability of infection, illness and diseases burden of gastrointestinal illness (GI) caused by RoV and NoV for both workers and visitors were estimated using QMRA and Monto-Carlo simulation technique. The annual mean concentration for RoV and NoV in sampling air of water spray park were 20and 1754, respectively. The %95 confidence interval (CI) calculated annual DALY indicator for RoV (Workers: 2.62 × 10−4–2.62 × 10−1, Visitors: 1.50 × 10−5–2.42 × 10−1) and NoV (Workers: 5.54 × 10−3–2.53 × 10−1; Visitors: 5.18 × 10−4–2.54 × 10−1) were significantly higher the recommended values by WHO and US EPA (10−6–10−4 DALY pppy). According to sensitivity analysis, exposure dose and disease burden per case (DBPC) were found as the most influencing factors on disease burden as a consequences of exposure to RoV and NoV, respectively. The comprehensive information on DALY and QMRA can aid authorities involved in risk assessment and recreational actions to adopt proper approach and mitigation actions to minimize the health risk.

Abstract In this pandemic SARS-CoV-2 crisis, any attempt to contain and eliminate the virus will also stop its spread and consequently decrease the risk of severe illness and death. While ozone treatment has been suggested as an effective disinfection process, no precise mechanism of action has been previously reported. This study aimed to further investigate the effect of ozone treatment on SARS-CoV-2. Therefore, virus collected from nasopharyngeal and oropharyngeal swab and sputum samples from symptomatic patients was exposed to ozone for different exposure times. The virus morphology and structure were monitored and analyzed through Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Atomic Absorption Spectroscopy (AAS), and ATR-FTIR. The obtained results showed that ozone treatment not only unsettles the virus morphology but also alters the virus proteins’ structure and conformation through amino acid disturbance and Zn ion release from the virus non-structural proteins. These results could provide a clearer pathway for virus elimination and therapeutics preparation.

Background: Detection of Leishmania RNA virus (LRV) in Old World Leishmania species and their possible role in the disease prognosis requires sensitive and specific methods, preferably independent of the viral genome. We aimed to develop an indirect immunofluorescence antibody (IFA) assay to detect LRV in the Old World Leishmania parasites. Methods: Clinical samples were collected from 86 cutaneous leishmaniasis (CL) patients in different endemic areas of CL in Iran, during 2017-2019. For antibody preparation, the viruses were obtained from sediment of an LRV-infected L. major culture-using freeze and thaw cycles followed by gradient cesium chloride centrifugation. The purified viruses were used to immunize a male 3-4 months rabbit. Various dilutions of the LRV-immunized rabbit's serum and a conjugated antibody were deployed to detect LRV in 48 isolates by IFA assay. Results: LRV virus was detected in four of the 48 CL cases using IFA method. Amplification of a partial fragment of RNA-dependent RNA polymerase (RdRp) gene from the isolates confirmed the IFA results. In phylogeny, the generated RdRp sequences from four isolates were grouped with the other Old World LRVs, but separate from L. aethiopica LRVs, which appeared as a highly supported distinct clade. Conclusion: Further optimization of this approach to detect the LRV directly in lesion scrapings can make it a more reliable tool for field studies and disclosing the virus's possible role in disseminating and unusual clinical features.

Meningitis is defined as an inflammation of the meninges, which are the protective membranes surrounding the brain and spinal cord. Aseptic meningitis is the term used to describe all forms of meningitis that are not caused by pyogenic bacteria. Aseptic meningitis can be caused by a variety of etiological agents. Infectious agents include viruses, fungi, and parasites. Viruses are regarded as a significant etiological agent of aseptic meningitis. The viral etiology of this disease exhibits variability across different age groups and countries. This study aimed to examine the prevalence of different viruses (enterovirus, mumps virus, and HSV-1) in cerebrospinal fluid (CSF) samples of children diagnosed with aseptic meningitis. A total of 58 cerebrospinal fluid (CSF) samples were obtained from patients suspected of having meningitis and admitted to Ali Asghar Hospital in Tehran during the 2019-2020 period. Nucleic acid extraction was conducted, and polymerase chain reaction (PCR) testing was performed to investigate the presence of various meningitis-causative viruses. A total of 32 patients (24 males and 8 females) were found to be infected with viruses. The most prevalent meningitis virus identified was enterovirus, accounting for 25.9% of cases (n=15). The mumps virus and herpes simplex virus (HSV) were identified in 11 (19%) and six (10.3%) patients, respectively. The most common clinical manifestations observed in children with aseptic meningitis were fever and vomiting. A statistically significant correlation was identified between term week and the occurrence of viral meningitis among patients infected with HSV and mumps (p-value = 0.04). Furthermore, a borderline relationship was observed between a history of surgery and viral meningitis. Enteroviruses represent a significant etiological agent of aseptic meningitis across a range of age groups. An accurate diagnosis of meningitis viruses, such as enteroviruses, will facilitate the implementation of appropriate and life-saving antiviral therapies, while reducing the overuse of antibiotics. [ABSTRACT FROM AUTHOR]

Objective: Leishmania RNA virus (LRV) is a double-stranded RNA (dsRNA) virus that circulates within many species of the Leishmania parasite. In this study, we aimed to investigate the presence of LRV2 circulating in Leishmania isolates in an old focus of ZCL located in northeastern of Iran. Methods: Leishmania isolates were collected from 85 patients that confirmed to have cutaneous leishmaniasis (CL) based on parasitological examination. To identify the Leishmania isolates, species-specific primer sets were applied for molecular identification. The presence of LRV2 was performed by RdRp-semi nested-PCR. The genetic diversity were calculated using MEGA and DnaSP. To assess haplotype diversity, 31 LRV2 strains in different regions were surveyed using analysis a 292-bp section of the RdRp sequences. Results: Out of 85 patients, 83 (97.6 %) were diagnosed with L. major and 2 (2.4 %) with L. tropica. LRV2 virus was detected in 59 (69.4%) of the CL cases. For the first time, LRV2 was reported in one L. tropica strain in Iran. The current LRV2 sequences indicated the highest similarities to an Old World LRV2. Moreover, 10 unique haplotypes were identified based on the analyzed sequences of the RdRp gene. Conclusions: Our results indicated the highest occurrence of Leishmania/LRV2 co-circulation in this known ZCL focus from northeastern Iran. Phylogenetic analyses of LRV2 sequences confirmed that these isolates belong to the order of LRV2 from the Old World. This study offered an insight into LRV2 haplotype that the informative issue can be used for genetic research of LRV2 in other regions.

Abstract 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.

Abstract 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

Currently, there are about 37 million people worldwide living with human immunodeficiency virus (HIV) /AIDS, with an estimated two million new cases per year globally. According to estimates from the World Health Organization (WHO), only 75% of the population with HIV know their status. Initially, HIV infection was associated with significantly increased rates of mortality and morbidity. However, the rapid advances in treatment and the advent of different classes of antiretroviral drugs over time have led to change the face of HIV/AIDS from a deadly infection to chronic and manageable disease. There is strong evidence that HIV-infected patients undergoing antiretroviral therapy have longer lives and are less likely to transmit infection to their sexual partners. Since the introduction of zidovudine in 1987 as the first antiretroviral drug, significant strides have been made in antiretroviral therapy. The introduction of potent antiretroviral drugs for the treatment of HIV infection has been one of the significant events in the evolution of modern medicine. Antiretroviral therapy refers to the use of drugs in the treatment of HIV. Generally, these drugs are categorized based on the steps of the HIV life cycle suppressed by them. There are six main classes of antiretroviral agents including nucleoside/ nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, co-receptor inhibitors, and integrase inhibitors. Combination antiretroviral therapy should be considered for HIV patients to achieve the highest viral suppression rate, and to reduce the risk of resistance development and morbidity and mortality associated with AIDS. Achieving and maintaining HIV viral load suppression among treated patients has remarkably increased over the last years due to the development of potent and well-tolerated agents which can be co-formulated as a once-daily single-tablet or fixed-dose combination for simplification. However, there are some limitations preventing patients to benefit from this treatment. The main goals of HIV therapy in the future are to overcome the limitations of current treatment, including side effects. This review will provide an overview of advances in the current antiretroviral drugs by focusing on their pharmacokinetics, mechanism of action, dosing recommendations, and adverse events for each drug class.

Background Rotavirus is the most prevalent cause of severe gastroenteritis, hospitalizations, and deaths among infants and young children, globally. No specific antiviral drug is available against rotavirus infection. Objective The current study aimed to assess the antiviral effect of human cathelicidin antimicrobial peptide LL-37 on rotavirus infection in vitro. Methods This study was conducted in the laboratory conditions of Iran University of Medical Sciences, in Tehran City, Iran. The neutral red assay was performed to assess the cytotoxicity of different concentrations of the peptide on the MA-104 cell line, and its antiviral activity was determined by TCID50 (50% tissue culture infective dose) assay. Findings According to the cytotoxicity results, viability maintained more than 90% up to the concentration of 50 μg/mL of LL-37 peptide. The antiviral assays results revealed that the concentration of 50 μg/mL LL-37 peptide could significantly reduce (3.36 log10 TCID50) the production of rotavirus progeny when administered before virus exposure (P= 0.0001). However, no inhibitory effect was detected after cell exposure to virus. Conclusion The obtained data suggested that LL-37 can be considered as a new antiviral agent for protecting infants and young children against gastroenteritis caused by rotaviruses. However, further in vivo investigations are required to confirm this finding.

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.

Background and Objectives: The viruses are the most common cause of eye infection. The most common viruses in conjunctivitis infection include Herpes simplex virus, Adeno virus and Entrovirus. It has been estimated that HSV1 causes 60-90% conjunctival infectionsin adults. Recurrent infection by HSV1 results in Herpes keratitis that is the most common cause for blindness in developing countries. Therefore, a prompt laboratory diagnosis is often very useful. Theaim of this study was to evaluate the prevalence of conjunctivitis infection by HSV-1 Hospital affiliated to Iran University of Medical Sciences (IUMS) in 2009.Methods: This descriptive cross-sectional study was doneon 100 tear film and eye swabs specimens from patient with symptoms of viral conjunctivitis. All samples werecollected in viral transport media (VTM) and inoculated in Vero cell line. Viral cytopatic effect was compared with control sample. HSV1 DNA wasdetected by polymerase chain reaction (PCR). Chi-square test was used to for data analysis (p

The present study was conducted to monitor the genotypes of circulating species A rotavirus (RVA) in Iran and investigate genetic linkages between specific RVA VP7, VP4, VP6, and NSP4 segments. For this purpose, 48 RVA strains were detected during the 2021–2022 seasons. The two combinations of G9P[4] and G9P[8] RVA strains were predominant. However, several other combinations of RVA also were detected. Based on the distribution of I and E genotypes (46 strains) with respect to G and P, the most common strains were G9P[4]‐I2‐E2 (19.5%), G9P[4]‐I2‐E1 (6.5%), G9P[4]‐I1‐E1 (4.3%), G9P[8]‐I1‐E1 (19.5%), and G9P[8]‐I2‐E2 (10.9%), which were followed by several other combinations of G and P RVA strains with different pattern of I‐E genotypes and also emerging, rare and uncommon strains. The present study described the continued circulation of G9 strains with the emergence of uncommon G9P[4] and G9P[8] reassortants with three and two different I‐E genotypes, respectively, which have not been reported previously in Iran. Our findings indicated that these uncommon strains exhibited a unique genotype pattern comprising a mixture of genogroup 1 and 2 genes and suggest the need for further analysis of rare, uncommon, and emerging strains of RVA at all 11 gene segments to determine intergenogroup and intragenotype reassortments. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but the pathogenesis is unclear. Host genetic background is one of the main factors influencing the patients' susceptibility to several viral infectious diseases. This study aimed to investigate the association between host genetic polymorphisms of two genes, including vitamin D receptor (VDR) and vitamin D binding protein (DBP), and susceptibility to COVID‐19 in a sample of the Iranian population. This case‐control study enrolled 188 hospitalized COVID‐19 patients as the case group and 218 suspected COVID‐19 patients with mild signs as the control group. The VDR (rs7975232, rs731236 and rs2228570) and DBP (rs7041) gene single nucleotide polymorphisms (SNPs) were genotyped by Polymerase Chain Reaction Restriction – Fragment Length Polymorphism (PCR‐RFLP) method. A significant association between rs2228570 SNP in the VDR gene and the susceptibility of COVID‐19 was found between case and control groups. The CT genotype (Heterozygous) of rs2228570 C > T polymorphism showed significant association with a 3.088 fold increased odds of COVID‐19 (p <.0001; adjusted OR: 3.088; 95% CI: 1.902–5.012). In addition, a significant association between CC genotype of rs2228570 CT polymorphism and increased odds of COVID‐19 in male and female groups (p =.001; adjusted OR: 3.125; 95% CI: 1.630–5.991 and p =.002; adjusted OR: 3.071; 95% CI: 1.485–6.354 respectively) were determined. Our results revealed no significant differences in the frequency of genotype and allele of VDR (rs7975232 and rs731236) and DBP (rs7041) between SARS‐CoV‐2‐infected patients and controls (p >.05). Our results showed that polymorphism of VDR (rs2228570) probably could influence individual susceptibility to COVID‐19. The polymorphisms of VDR (rs7975232 and rs731236) and DBP (rs7041) were not associated with SARS‐CoV‐2 infection susceptibility. [ABSTRACT FROM AUTHOR]

Background: Detection of Leishmania RNA virus (LRV) in Old World Leishmania species and their possible role in the disease prognosis requires sensitive and specific methods, preferably independent of the viral genome. We aimed to develop an indirect immunofluorescence antibody (IFA) assay to detect LRV in the Old World Leishmania parasites. Methods: Clinical samples were collected from 86 cutaneous leishmaniasis (CL) patients in different endemic areas of CL in Iran, during 2017-2019. For antibody preparation, the viruses were obtained from sediment of an LRV-infected L. major culture-using freeze and thaw cycles followed by gradient cesium chloride centrifugation. The purified viruses were used to immunize a male 3-4 months rabbit. Various dilutions of the LRV-immunized rabbit's serum and a conjugated antibody were deployed to detect LRV in 48 isolates by IFA assay. Results: LRV virus was detected in four of the 48 CL cases using IFA method. Amplification of a partial fragment of RNA-dependent RNA polymerase (RdRp) gene from the isolates confirmed the IFA results. In phylogeny, the generated RdRp sequences from four isolates were grouped with the other Old World LRVs, but separate from L. aethiopica LRVs, which appeared as a highly supported distinct clade. Conclusion: Further optimization of this approach to detect the LRV directly in lesion scrapings can make it a more reliable tool for field studies and disclosing the virus's possible role in disseminating and unusual clinical features. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer around the world. Since this cancer is highly resistant to the existing treatments, we used a novel method, which selectively targets HCC cancer cells to improve the treatment process. As normal cells are resistant to reovirus replication, we used oncolytic reoviruses, which can infect, replicate in, and destroy cancer cells. In this study, the effects of oncolytic human reoviruses on cancer cells, derived from HCC biopsies, were investigated. Methods: First, reoviruses were purified. Then a plaque assay was performed to estimate the number of viruses and determine the multiplicity of infection (MOI). To evaluate the effects of reoviruses on cancer cells derived from HCC biopsies, replication of reovirus RNA, viral protein production, cytopathic effects (CPE), and cancer cell viability were assessed at different intervals post-infection. Results: Replication of reovirus RNA and viral protein production were detected in cancer cells. Also, different levels of viral protein production, CPE, cytotoxicity, and cancer cell viability were observed at different intervals post-infection with human reoviruses. In contrast, normal human fibroblasts, which were used as negative control, remained unchanged. Conclusions: For the first time, the effects of human reoviruses on HCC biopsies were investigated. The results showed that human reoviruses could replicate in and destroy cancer cells derived from HCC biopsies. Overall, human reoviruses can be potentially used for the treatment of HCC. [ABSTRACT FROM AUTHOR]

From a health prospective, it is critical to provide a comprehensive model which integrates all the parameters involved in virus transmission and its consequences on human body. In order to estimate the health risks, for workers and residents, associated with an exposure airborne viruses emitted from a wastewater treatment (WWTP), the concentration levels of viruses in emitted bioaerosols over a twelve-month period were measured by real-time polymerase chain reaction (RT-PCR). A combined Gaussian plum dispersion model and quantitative microbial risk assessment (QMRA) with Monte-Carlo simulation served as suitable explanatory tools to estimate the risk of acquiring gastrointestinal illness (GI) due to exposure to air containing Rotavirus (RoV) and Norovirus (NoV) bioaerosols. Additionally, DALY metric was applied to quantify the disability and mortality for workers and residents. RoV and NoV were detected above aeration tank with annual mean concentration 27 and 3099 (Viruses/m3.h), respectively. The medium calculated DALY indicator based on viral loads in contaminant source (RoV:5.76 × 10−2 and NoV:1.23 × 10−1) and estimated in different distances away (300–1000 m) (RoV:2.87 × 10−2- 2.75 × 10−2 and NoV:1.14 × 10−1-1.13 × 10−1) were markedly higher than the threshold values recommended by US EPA (10−4 DALY pppy) and WHO (10−6 DALY pppy). The sensitivity analysis highlighted dose exposure and disease burden per case (DBPC) as two most influential factors for both workers and residents following exposure to two pathogens of concern. Due to high resistance and high concentration in the environment, the presence of RoV and NoV can intensify the consequences of diarrhea especially for children under five years of age; A comprehensible and transparent presentation of DALYs and QMRA can help decision makers and responsibilities to justify the priorities of exposure to wastewater in comparison with other risks of daily life. Image 1 • RoV and NoV were monitored with annual mean concentration 27 and 3099 (Viruses/m3h), respectively. • Pinf for RoV(8.3 × 10−3-2.3 × 10−3) and NoV(9.8 × 10−2-9.4 × 10−2) decreased at distances 300–1000 m. • The medium DALY for workers for exposure to RoV and NoV were 5.7 × 10−2 and1.2 × 10−1. Capsule: Proposing a comprehensive model for measured RoV and NoV in WWTP air and their atmospheric dispersion to calculate corresponding QMRA and DALY for workers and residents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (TCID50) 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 log10 TCID50 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. [ABSTRACT FROM AUTHOR]

Background: Wide distribution and low half-life of acyclovir has led to a high dose consumption of the drug. Recent studies have shown that encapsulation of acyclovir in nano-carriers can increase effectiveness and decrease its side effects. We investigated the inhibitory effect of acyclovir loaded nano-niosomes against herpes simplex virus type-1 (HSV-1) in cell culture. Methods: In-vitro cytotoxicity study of empty niosomes (E-N), acyclovir loaded niosomes (ACV-N) and ACV as a free drug against HeLa cell line was performed by MTT assay and the viral titers was tested by TCID50 assay. Results: The results indicated that a significant higher antiviral activity for acyclovir loaded nano-niosomes of about 3 times in comparison with free drug. Conclusion: The results of this study revealed ACV-N have a higher antiviral activity compared with free drug; it could be a suitable carrier for delivery of acyclovir in the treatment of HSV-1 infections. [ABSTRACT FROM AUTHOR]

Background: Limited sources of fresh water necessitate the application of health policies for treatment and decontamination of human sewage for further use. A wide variety of infectious agents, including bacteria, fungi, parasites, and viruses, can be found in sewage. Enteric viruses such as hepatitis A virus (HAV) can survive the current treatments and infect susceptible hosts. Objectives: This study aimed to evaluate HAV contamination in human sewage before and after treatment in the wastewater treatment plant of Ekbatan town in Tehran, Iran, and analyze the phylogenetic properties of the identified viruses. Methods: Over a 12-month period, we collected the wastewater samples including influent, before chlorination, and effluent, from the wastewater treatment plant of Ekbatan town in Tehran, Iran. Ribonucleic acid (RNA) extraction, complementary deoxyribonucleic acid (cDNA) synthesis, and semi-nested polymerase chain reaction (PCR) were performed to identify HAV contamination. Phylogenetic analysis was performed to investigate subgenotypes of the virus. Results: HAV was detected in all influents and samples before chlorination, while the virus was detected in 50% of the effluent samples. All detected viruses belonged to subgenotype IB. Conclusions: Investigating the presence of HAV in sewage provides a general picture of the virus spread in the population of interest. HAV was detected in all influent samples, indicating that the infection is endemic in this area all year round. This also indicates the inability of the current treatment protocols in virus removal, which can be a threat to the public health. [ABSTRACT FROM AUTHOR]

Background: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. Methods: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. Results: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. Conclusion: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Background: Complete SARS-CoV-2 genome sequencing in the early phase of the outbreak in Iran showed two independent viral entries. Subsequently, as part of a genome surveillance project, we aimed to characterize the genetic diversity of SARS-CoV-2 in Iran over one year after emerging. Methods: We provided 319 SARS-CoV-2 whole-genome sequences used to monitor circulating lineages in March 2020-May 2021 time interval. Results: The temporal dynamics of major SARS-CoV-2 clades/lineages circulating in Iran is comparable to the global perspective and represent the 19A clade (B.4) dominating the first disease wave, followed by 20A (B.1.36), 20B (B.1.1.413), 20I (B.1.1.7), leading the second, third and fourth waves, respectively. We observed a mixture of circulating B.1.36, B.1.1.413, B.1.1.7 lineages in winter 2021, paralleled in a fading manner for B.1.36/B.1.1.413 and a growing rise for B.1.1.7, prompting the fourth outbreak. Entry of the Delta variant, leading to the fifth disease wave in summer 2021, was detected in April 2021. This study highlights three lineages as hallmarks of the SARS-CoV-2 outbreak in Iran; B4, dominating early periods of the epidemic, B.1.1.413 (B.1.1 with the combination of [D138Y-S477N-D614G] spike mutations) as a characterizing lineage in Iran, and the co-occurrence of [I100T-L699I] spike mutations in half of B.1.1.7 sequences mediating the fourth peak. It also designates the renowned combination of G and GR clades' mutations as the top recurrent mutations. Conclusion: In brief, we provided a real-time and comprehensive picture of the SARS-CoV-2 genetic diversity in Iran and shed light on the SARS-CoV-2 transmission and circulation on the regional scale. [ABSTRACT FROM AUTHOR]

Leishmania RNA virus (LRV) is a double-strand RNA virus that was first detected in members of the Leishmania viannia in the New World. The present study aimed to investigate the presence of LRV in the Leishmania species isolated from cutaneous leishmaniasis (CL) patients and rodents as reservoirs in Isfahan province an old zoonotic CL focus, center of Iran. Totally, 85 samples were collected from CL patients (n = 80) and rodent reservoirs (n = 5) from different regions of Isfahan province. Species identification was determined using the PCR-RFLP method. Viral dsRNA was extracted and for observation of 5.3 kb dsRNA on an agarose gel. The presence of LRV was surveyed using the Semi-nested PCR method. For phylogenetic analyzes, 6 samples of 13 isolates were sequenced and a phylogenetic tree was drawn by MEGA7 version 7.0.26. Of 80 Leishmania isolates recovered from the patients with CL, 79 and only one were identified as L. major and L. tropica , respectively. Also, the PCR assays detected four L. major and one L. turanica in five assessed Rhombomys opimus as the rodent reservoirs. LRV was detected only in Leishmania species isolated from 13 species of 85 (15.3%) CL including (L. major , n = 12) and (L. tropica , n = 1). Phylogenetic analysis showed that they were belonged to LRV2 and had the highest similarity with Iranian reference LRV2 in GenBank. Our results showed that the LRV2 was present in cutaneous Leishmania species in Isfahan province is the most historical and touristic province of Iran. In the study LRV was not reported from rodent reservoirs, it may be due to the small sample size. Phylogenetic analysis of current sequences demonstrated that these isolates belong to the registered LRV2 of the Old World. • Leishmania RNA Virus 2 was detected in 13 (15.3%) of cutaneous leishmaniasis isolates studied. • Leishmania RNA Virus 2 in one L. tropica in Isfahan province, Iran was reported. • Our sequences analysis demonstrated LRV2 isolated from Isfahan are genetically similar to other LRV2 from the Old World [ABSTRACT FROM AUTHOR]

Background: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings., Methods: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021., Results: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants., Conclusion: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

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.)

Background: The emergence of drug-resistant strains of herpes simplex virus type 1 (HSV-1) has been increasingly reported. Therefore, attempts to discover new antiviral agents in particular from natural compounds are required. In this study, we evaluated the possible inhibitory effects of hydroalcoholic extract of Sambucus ebulus ( S. ebulus ) against HSV-1. Methods: S. ebulus extract was produced by maceration method. MTT assay was used to evaluate the cytotoxicity effects of the S. ebulus extract; also, antiviral effects were measured both by test TCID50 and quantitative real-time PCR methods. To study the inhibitory impact of S. ebulus extract on the expression of HSV-1 antigens, indirect immunofluorescence assay (IFA) was also performed. All analyses were performed using the GraphPad Prism software v. 7.0. Results: In the postexposure assay of HSV-1 with S. ebulus extract at the highest nontoxic concentration (75 μg/mL), S. ebulus extract led to inhibition rates of 91.2%, based on the quantitative real-time PCR assay results (p<0.001). Also, in the immunofluorescence assay, a significant reduction was observed in fluorescence emission intensity in HSV-1-infected cell treated with S. ebulus extract led to inhibition rates of 91.2%, based on the quantitative real-time PCR assay results (p<0.001). Also, in the immunofluorescence assay, a significant reduction was observed in fluorescence emission intensity in HSV-1-infected cell treated with S. ebulus extract is a novel and effective natural compound in reducing HSV-1 titer and future studies should be conducted to discover the complete mechanism of antiviral effect of this natural compound.Conclusion: S. ebulus extract is a novel and effective natural compound in reducing HSV-1 titer and future studies should be conducted to discover the complete mechanism of antiviral effect of this natural compound., (© 2021 Iran University of Medical Sciences.)

Background: Epstein-Barr virus (EBV) is associated with different malignant diseases, such as Hodgkin lymphoma (HL) and lymphoproliferative disorders. Patients with hematologic malignancies by variable severity could be suspected for the infection with different types of this virus. This preliminary study reported the genotyping and related viral load of Epstein-Barr virus in Iranian patients with hematologic malignancies for estimation of possible factors affecting malignancy., Methods: Peripheral blood mononuclear cells (PBMC) of HL (n=20), NHL (n=29), acute lymphocytic leukemia (ALL) (n=18) and chronic lymphocytic leukemia (CLL) (n=12) were obtained. After DNA extraction, a nested-PCR and a conventional-PCR targeting EBNA-2 and EBNA-3C genes were performed. A real-time PCR assay for viral load quantitation carried out. Standard curve analysis used for evaluation of amplification specificity., Results: Of 79 included patients, 34 (43%) were EBV positive. There were 23.5% (8/34), 38.2% (13/34), 23.5% (8/34), 14.8% (5/34) in HL, NHL, ALL and CLL groups, respectively. Also, the main genotype was genotype I (91.2%) which it follows by 8.8% (3/34) genotype II. The real-time PCR assay showed the mean viral load ± std. deviation was 2.75×105 ± 1.202×106 copies/μg DNA and the higher viral load was seen in NHL patients., Conclusion: This preliminary investigation in Iran shows that the main EBV genotype into our region probably is genotype I (91.2%) which it is similar to others. We could not find any statistically significant association between the virus infection and viral load with any specific disease and patients' demographic data. , .