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Background and Objectives: Iran, like most other countries in the world, is always threatened with global epidemics and pandemics of influenza. The purpose of this study was to review the influenza surveillance system in Iran. Methods: Data of this study were obtained from the surveillance system of the Center for Communicable Disease Control, the review of records, documents, books and published articles and also interviews with process owners and experts of influenza surveillance in 2017-2019. Results: Influenza surveillance in Iran Currently, a combination of surveillance methods, including caring for patients, laboratory care, hospital care and surveillance of respiratory disease epidemics and also border surveillance. Reporting of human influenza outbreaks, as well as suspected avian flu as main notifiable diseases carried out through telephone. For each suspect case, in addition to taking and sending a sample to diagnose and also detect subtypes of the virus, medical treatment is immediately initiated and tracking of possible contacts is also done. Conclusion: Although there is currently good coherence in the surveillance of influenza in Iran, but based on concerns about the emergence of influenza pandemics in the future, and considering the possible genetic variation of the flu viruses, the tracking of the flu virus circulation along with updating surveillance system especially emphasizing methods and formulas for rapid identification of disease outbreaks, as well as providing better health care and treatment is essential.

Objective: Measles is one of the acute and contagious diseases of human, and according to the estimation of the world health organization (WHO), it may be eradicated by the year 2010. Therefore, diagnosis of measles is emphasized by using quick and sensitive methods for control and prevention of measles. Methods: Various methods are used to diagnose antibody against measles virus, include hemagglutination inhibition (HI), enzyme immunoassay (EIA), plaque reduction (PR) and neutralization test (NT). One of the methods is dot-immunoassay (DIA). In this method, nitrocellulose paper is used as solid phase instead of microplate. Findings: In this study, DIA in comparison to HI had 98.8% sensitivity and 85% specificity, and in comparison to EIA had 96.5%, 90% sensitivity and specificity respectively. Conclusion: This technique has advantages such as sensitivity, high specificity, low cost and speed.

Background: Respiratory virus infections in children are a leading cause of morbidity and mortality worldwide. Methods: A total of 897 clinical specimens were collected from February 2007 to January 2008 and transported to the Na­tional Influenza Center. Two hundred and two samples belonged to children under the age of six from 897 specimens, de­scribed above, were selected. Then they were tested for influenza virus types and subtypes by real time PCR assay subse­quently, the specimens were tested for RSV and hMPV by hemi-nested multiplex PCR and parainfluenza viruses type 1-4 by hemi-nested multiplex PCR and adenovirus by hemi-nested PCR. Results: The throat swab was taken from the Kawasaki case with the history of chicken`s contact. The specimen was tested for all influenza subtypes especially H5N1 and the results were negative. Meanwhile PCR was done for screening of other respira­tory viruses that results came out positive for RSV and hMPV. Conclusion: In the present study, we demonstrated the possibility to detect dual infection caused by RSV and hMPV, but be­cause of the extravagant pattern of this case, more investigation is suggested specially on Kawasaki patients.

rotavirus infections are one of the etiological agents of infantile and children,s gastroenteritis.in this study 450 fecal samples from children under 2 years old from cities of Tehran nad Zahedan were collected.of these specimens.73 samples which were cosidered as moderately positive(++) by ELISA were selected.SDS-PAGE analysis showed fifty six different rotavirus electrophoretypes from which eight and forth eight patterns belonged to Zahedan and Tehran samples respectively.basically,from eight patterns of Zahedan samples,five(71.5%) were related to L and two (28.5%) to S rotavirus group A which includes seven different electrophoretypes.from forty eight patterns of Tehran samples,thirth six belonged to L series with twenty six defferent electrophoretypes (76.5) and twelve to S types with eight different electrophoretypes (23.5%).in addition, a mixed S and L electrophoretype and two abnormal genom of rotavirus with the pattern of 2&3&3&4 were identified.different electrophoretype of rotaviruses in Tehran and Zahedan showed a high diversity in comparison with electrophoretic patterns from other countries.

Background and objectives: Each year, Enteroviruses infect millions of people and cause different diseases. The agents are usually detected using cell culture. RD (Rhabdomyosarcoma) and L20B (L cells) are among the recommended cells by the World Health Organisation (WHO) for this purpose. Even though cell culture is the most common method used in diagnosing Enteroviruses in stool specimens, this particular method poses some problems, which include false positive or negative results, lack of a unique cell line for diagnosing all Enterovirus types in addition to being time consuming. For these reasons, an attempt was made to find better techniques of Enterovirus detection. RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) is a technique used in place of the cell culture method. In this study, the cell culture method was compared with RT-PCR for detection of Enteroviruses in stool specimens. Material and method: First, the chloroform treated stool samples were inoculated onto five cell lines, including RD, L20B, Hep-2 (Human Epidermoid carcinoma cell line), Vero (Verde Reno) and GMK (Green Monkey Kidney). The results were then compared with data from Enterovirus detection using the RT-PCR technique. Results and conclusion: The difference between RT-PCR and cell culture results was significant. Enteroviruses were detected in 24% of specimens using RT-PCR while cell lines could isolate Enteroviruses in just 14.4% of the samples.

"nBackground: Molecular epidemiology of measles virus (MV) is important, not only to measure the success of measles vaccination programs but also to monitor the circulation and elimination of the virus worldwide. In this study, we compared MV obtained from patients before the 2003 mass vaccination MR campaign and viruses detected after 2003 until 2008 in Iran."nMethods: The nucleoprotein (N) gene of 29 MV strains circulating in Iran between 2002 and 2008 were amplified by RT-PCR and subjected to sequence and phylogenetic analysis."nResults: Molecular characterization of MV studied here revealed that although the outbreaks in Iran were associated with MV genotype D4, the isolated viruses clearly belonged to several different lineages. Maximum and minimum homology within the 29 Iranian strains in our study was100% and 94.9% within the carboxyl terminus of the N gene, respectively. Using ClustalX program, the alignment of Iranian MV sequences showed nine lineages."nConclusion: This study provides the usefulness of MV sequence analysis for the demonstration of local interruption of indigenous strain transmission as well as providing a valuable means for monitoring the elimination processes of MV control.

"nBackground: Parvovirus B19 (B19) is the only member of the family Parvoviridae associated with human infection. Al­though there are some studies to estimate the immunity to parvovirus in various populations but there is no seroepidemiologi­cal sur­vey from Iran until now thus the age-specific immunity to human parvovirus infection was esti­mated."nMethods: A subset sample of 1500 study subjects in 2004 after Measles and Rubella mass campaign was selected from the original samples of 5000 sera kept at the Department of Virology in Tehran University of Medical Sciences. All sera were tested by a commercial ELISA kit."nResults: Totally, 1303 (86.6%) of 1500 study subjects were seropositive for B19 IgG antibody. The seropositive rate of males and females were 85.3% and 88%, respectively (P= 0.129). The overall B19 seropositive rates in rural and urban were 84.3% and 88%, respectively (P= 0.044). The seropositive rates were found to increase significantly with age and ranged from 79.3% in 5-9 year old group to 93.5% in 20-25 yr old group (P= 0.000)."nConclusion: Our results indicate that in spite of high prevalence of B19 antibody the importance of routine diagnosis of B19 infection in order to elucidate the etiology of some unexplained 'exanthemata diseases' especially in measles elimina­tion and eradication phase is needed.

Background: Influenza A viruses bearing all known HA and NA subtypes have been isolated from avian hosts: but only the A/H1N1,A/H2N2 and A/H3N2 influenza subtypes have been associated with widespread epidemics in humans un­til now .While influenza B detected only in humans. Subtype H5 infection in humans occurred for the first time dur­ing 1997-1998 in Hong Kong, then China in 2003, Vietnam and Thailand in 2004 and continued to 2005-2006 in Tur­key and Egypt. In this study a Multiplex Nested RT-PCR was developed for simultaneous detection of influenza virus A and B in clinical samples. Methods: Throat swab and throat wash was collected between October 2005 and September 2006 from 689 patients with a suspected influenza virus infection. Samples were transported to the National Influenza Center (Tehran Univer­sity of Medical Science, School of Public Health). Each sample is divided into two parts in order to virus isolation and nested RT-PCR. Results: The RT-PCR detected in 75 cases of influenza A and B, compared to 26 cases by virus isolation and 74 cases are positive by RT-PCR. In total, 50 out of 74 RT-PCR positive specimens were negative by virus isolation. The RT-PCR provides a sensitive and specific method for detecting and typing influenza viruses A and B. Conclusion: The RT-PCR provides a sensitive and specific method for detecting and typing influenza viruses A and B. Multi­plex RT-PCR can also be used to accurately detect more than one viral template in the same reaction mixture, allow­ing viral confections to be identified with the same respiratory specimen.

Measles is an infectious febrile sickness caused by the measles virus (MeV). Despite an effective vaccine, regional elimination of measles remains a global priority and still faces challenges. To estimate community protection against measles, sensitive tests are needed to identify measles-specific antibodies. The enzyme-linked immunosorbent assay (ELISA) is the standard test for assessing immunity but may fail to detect weak antibody responses in vaccinated populations. The plaque reduction neutralization test (PRNT), is the gold standard test for the assessment of protective antibody levels, however, it is not suitable for routine use. This study validated the focus reduction neutralization test (FRNT) as an alternative. In eight assay runs, fifty serum samples were analyzed in triplicate using PRNT, FRNT, and ELISA. Data analysis revealed that 38 samples were positive by PRNT, 37 by FRNT, and 19 by ELISA. The results showed that ELISA was not sensitive enough to identify low levels of anti-measles antibodies and showed weak agreement with neutralization assays. In contrast, the two neutralization assays had a perfect correlation and similar sensitivity. FRNT appears to be a suitable alternative to PRNT for characterizing immunological responses and vaccination efficacy. Our results highlight the necessity of validating negative and equivocal ELISA results through neutralization methods, during the elimination phases., Competing Interests: Declaration of competing interest None., (Copyright © 2024 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: The seroprevalence of antibodies against measles, mumps, and rubella (MMR) was evaluated 17 years following a mass vaccination campaign in individuals aged 2 to 22 years who had received routine immunization but were not eligible for an extended immunization program., Methods: Samples were acquired from Iran's National Measles Laboratory (NML), with individuals showing positive IgM results excluded. Out of the samples collected in 2020, a random selection of 290 serum samples was chosen, representing individuals between the ages of 2 and 22 years from diverse regions in the country. These samples were subjected to analysis using an enzyme-linked immunosorbent assay (ELISA) to quantify specific IgG antibodies against MMR., Results: The seroprevalence rates of antibodies for measles, mumps, and rubella were determined to be 76.2%, 89.3%, and 76.9%, respectively. Younger age groups exhibited higher seropositivity rates for measles and mumps, whereas the 7- to 11-year-old group demonstrated the highest seropositivity rate for rubella. A reduction in antibody status was observed from younger to older age groups, particularly those aged 17-22., Conclusion: The study unveiled suboptimal antibody levels for measles and rubella, highlighting the necessity for further investigation and potential adjustments to future vaccination strategies. Moreover, the decline in antibody status post-vaccination can accumulate in seronegative individuals over time, elevating the risk of outbreaks., (© 2024. The Author(s).)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that uses angiotensin converting enzyme 2 (ACE2), a pivotal member of the renin-angiotensin system (RAS), as its cell-entry receptor. Another member of the RAS, angiotensin II (Ang II), is the major biologically active component in this system. There is growing evidence suggesting that serum miRNAs could serve as prognostic biomarkers for SARS-CoV-2 infection and regulate ACE2 expression. Therefore, the aim of this study is to evaluate the changes in the serum levels of sACE2 and Ang II, as well as the expression level of miR-141-3p and miR-421 in SARS-CoV-2 positive and negative subjects., Methods: In the present study, the serum levels of sACE2 and Ang II were measured in 94 SARS-CoV-2 positive patients and 94 SARS-CoV-2 negative subjects with some symptoms similar to those of SARS-CoV-2 positive patients using the ELISA method. In addition, the expression level of miR-141-3p and miR-421 as ACE2 regulators and biomarkers was evaluated using quantitative real-time PCR (qRT-PCR) method., Results: The mean serum sACE2 concentration in the SARS-CoV-2-positive group was 3.268 ± 0.410 ng/ml, whereas in the SARS-CoV-2 negative group, it was 3.564 ± 0.437 ng/ml. Additionally, the mean serum Ang II level in the SARS-CoV-2 positive and negative groups were 60.67 ± 6.192 ng/L and 67.97 ± 6.837 ng/L, respectively. However, there was no significant difference in the serum levels of sACE2 (P value: 0.516) and Ang II (P value: 0.134) between the SARS-CoV-2 positive and negative groups. Meanwhile, our findings indicated that the expression levels of miR-141-3p and miR-421 in SARS-CoV-2 positive group were significantly lower and higher than SARS-CoV-2 negative group, respectively (P value < 0.001)., Conclusions: Taken together, the results of this study showed that the serum levels of sACE2 and Ang II in SARS-CoV-2 positive and negative subjects were not significantly different, but the expression levels of miR-141-3p and miR-421 were altered in SARS-CoV-2 positive patients which need more investigation to be used as biomarkers for COVID-19 diagnosis., (© 2024. The Author(s).)

Background: This study aims to explore the potential of utilizing the expression levels of cannabinoid receptor 2 (CB2), μ-opioid receptor (MOR), MCP-1, IL-17, IFN-γ, and osteopontin as predictors for the severity of SARS-CoV-2 infection. The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2., Methods: Using quantitative Real-time PCR, we analyzed the gene expression levels of CB2 and MOR in nasopharynx specimens obtained from patients diagnosed with SARS-CoV-2 infection, with 46 individuals classified as having severe symptoms and 46 as non-severe. Additionally, we measured the circulating levels of MCP-1, IL-17, IFN-γ, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups., Results: Our results demonstrated a significant increase in MOR gene expression in the epithelium of patients with severe infection. The expression of CB2 receptor was also elevated in both male and female patients with severe symptoms. Furthermore, we observed concurrent rises in MCP-1, IL-17, IFN-γ, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-γ, and osteopontin showed strong predictive abilities in distinguishing between patients with varying degrees of SARS-CoV-2 severity. Moreover, we identified a significant correlation between CB2 expression and the levels of MOR, MCP-1, osteopontin, and IFN-γ., Conclusions: These results underline the interconnected nature of molecular mediators in a sequential manner, suggesting that their overexpression may play a role in the development of SARS-CoV-2 infections., (© 2024. The Author(s).)

Background: Following rubella virus control, the most important cause of congenital infections is human cytomegalovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non-primary maternal infections. The present study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran., Methods: Out of 1629 collected infants' serum samples suspected of CRS but negative for rubella IgM, 524 samples were selected regarding cCMV complications. These samples were divided into two age groups: 1- one month and younger, 2- older than 1 month up to one year. Anti-HCMV IgM detection was performed on these serums. Then HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results in IgM detection., Results: Herein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM, 12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one month to one year was 14.5%. Identified genotypes in this study were gB-1(63.63%), gB2 (18.18%), and gB3 (18.18%), respectively., Conclusions: This comprehensive study was performed on serum samples of symptomatic infants clinically suspected of cCMV from all over Iran. There was a good correlation between serology findings and PCR., (© 2024. The Author(s).)

Background and Objectives: Epstein-Barr virus (EBV) infection is ubiquitous all around the world. Tonsils seem to be candidate replication sites for EBV, and these tissues can be infected acutely or chronically. Some studies reported an association between EBV infection and tonsillar hypertrophy. In this study, we aimed to evaluate the presence and copy number of the EBV genome in tonsil tissue specimens of patients with tonsillar hypertrophy., Methods: A cross-sectional study was performed on 50 fresh tonsil tissue samples from children, who underwent tonsillectomy because of tonsillar hypertrophy. Patients' tonsil tissues were evaluated using real-time polymerase chain reaction for EBV genome and viral load. Finally, the results were analyzed using SPSS software., Results: EBV genome was detected in 58% (29/50) of tonsillar tissues. The relationship between EBV genome detection rate and age groups was in the statistical significance range ( P  = 0.051). Among 29 positive cases, the average EBV viral load was (3.1 × 10 5 ) copy/g ± (0.5 × 10 5 ) copy/g. No significant difference was observed among different sex and age groups for EBV viral load., Conclusion: Herein, EBV genome detection could support the colonization of EBV in the tonsils, which may have a direct or indirect association with the pathogenesis of tonsillar hypertrophy., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. World Journal of Otorhinolaryngology ‐ Head and Neck Surgery published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Background: Whole viral genome sequencing with next generation sequencing (NGS) technique is useful tool for determining the diversity of variants and mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study we have attempted to characterize the mutations and circulating variants of the SARSCoV-2 genome during the 4 th wave of COVID-19 pandemic in Tehran, Iran in 2021., Methods: We performed complete genome sequencing of 15 SARS-CoV-2 detected from 15 COVID-19 patients during the 4 th wave of COVID-19 pandemic with NGS. Three groups of the patients at the beginning, middle and the end of the 4 th wave were compared together., Results: We detected alpha and delta variants during the 4 th wave of the pandemic. The results illustrated a dominance of amino acid substitution D614G in spike, and the most frequent mutants were N-R203K, G204R, S235F, nsp12-P323L, nsp6-G106del, G107del and F108del., Conclusion: The detection of the virus mutations is a useful procedure for identifying the virus behavior and its genetic evolution in order to improve the efficacy of the monitoring strategies and therapeutic measures., (Copyright© 2023 Ahmadi et al. Published by Tehran University of Medical Sciences.)

Background: The role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection., Methods: 15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe [N = 40] and non-severe [N = 40] confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups., Results: The expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection., Conclusion: The results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Human orthopneumovirus (HOPV) or respiratory syncytial virus (RSV) is one of the important causes of acute respiratory infections (ARIs) during the cold months of the year worldwide. Many countries have reported an absence of ARIs due to HOPV during the winter of 2020-2021 associated with preventive measures to reduce the spread of SARS-CoV2. However, with the reduction of COVID-19 public health restrictions and the absence of immunity in the community due to the lack of exposure in the previous season, many countries had a delayed HOPV outbreak. Here we reported the impact of COVID-19 on the changing pattern of HOPV infection in Iran., Methods: Throat and nasopharyngeal swab samples were collected from patients (children and adults) with ARIs and sent to the Iran National Influenza Center. After RNA extraction, Real time RT-PCR was performed for HOPV detection., Results: In 260 samples collected from patients with ARIs in three different groups, which included children in March 2021, pilgrims in July 2022, and outpatients during November and December 2022, no HOPV was detected in any group., Conclusions: The lack of HOPV activity in Iran during the winter of 2020-2021 and then the resurgence in spring 2022 and again the absence of activity in summer and autumn 2022 was extraordinary in the HOPV epidemiology, and probably due to the implementation of public health non-pharmaceutical interventions to reduce the spread of SARS-CoV2. Although it is not possible to keep such restrictions, similar methods can be taken to control outbreaks caused by respiratory viruses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background and Aims: Real-time reverse-transcriptase polymerase chain reaction (real-time RT-PCR) is the gold standard test for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, when the test result is near the detection limit of the assay the possibility of getting false positive or negative results is high. In addition, it might result in single target gene positive (STGP) results which should be interpreted with caution., Methods: This study was performed on 29,962 nasal swabs from July 1 to August 31, 2020. Ct values less than 40 for each or both of N and RdRp genes were recommended to be selected as positive. Positive samples for one gene with the Ct s more than 35 were rechecked by adding more templates., Results: The results showed that 1016 (3.39%) samples were positive just for one gene with high Ct values. The results of the second reactions showed that 325 (31.99%) samples were positive for both N and RdRp which were reported positive, 301 (29.65%) were positive only for one gene which were considered as suspicious cases and resampling was suggested for them. Finally, 390 (38.385%) samples were negative for both genes., Conclusion: In conclusion, tracking weak positive results of SARS-CoV-2 real-time RT-PCR revealed that most of the individuals who were STGP clean the infection completely in less than a week which showed they were in the convalescent phase of infection. However, some of them who were in the beginning of infection showed a decrease in Ct value during a week, so they could spread the virus in the society., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Cervical cancer represents one of the most prevalent cancers among women worldwide, particularly in low- and middle-income nations. Oncolytic viruses (OVs) can infect cancer cells selectively and lethally without harming normal cells. Respiratory syncytial virus (RSV) is an oncolytic virus for anticancer therapy because of its propensity to multiply within tumor cells. This research aimed to assess the in vitro antitumor activities and molecular basis processes of the oncolytic RSV-A2 on the TC-1 cancer cells as a model for HPV‑related cervical cancers., Methods: Cellular proliferation (MTT) and lactate dehydrogenase (LDH) release assays were used to investigate the catalytic impacts of RSV-A2 by the ELISA method. Real-time PCR and flow cytometry assays were utilized to assess apoptosis, autophagy, intracellular concentrations of reactive oxygen species (ROS), and cell cycle inhibition., Results: Our MTT and LDH results demonstrated that TC-1 cell viability after oncolytic RSV-A2 treatment was MOI-dependently and altered significantly with increasing RSV-A2 virus multiplicity of infection (MOI). Other findings showed that the RSV-A2 potentially resulted in apoptosis and autophagy induction, caspase-3 activation, ROS generation, and cell cycle inhibition in the TC-1 cell line. Real-time PCR assay revealed that RSV-A2 infection significantly elevated the Bax and decreased the Bcl2 expression., Conclusions: The results indicated that oncolytic RSV-A2 has cytotoxic and inhibiting effects on HPV-associated cervical cancer cells. Our findings revealed that RSV-A2 is a promising treatment candidate for cervical cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Post-transplant human cytomegalovirus (HCMV) viremia has been linked to adverse "indirect effects" among transplant patients. HCMV-created immunomodulatory mechanisms could be associated with the indirect effects., Objective: In the present study, the RNA-Seq whole transcriptome of renal transplant (RT) patients was analyzed to seek the underlying pathobiologic pathways associated with the long-term indirect effects of HCMV., Methods: To investigate the activated biological pathways in HCMV infection, total RNA was extracted from PBMCs of 2 RT patients with active HCMV and 2 RT patients without infection and then were sequenced using RNA-Seq. The resulted raw data were analyzed by conventional RNA-Seq software to determine the Differentially Expressed Genes (DEGs). Afterward, Gene Ontology (GO) and pathway enrichment analyses were conducted to determine the enriched pathways and biological processes by DEGs. Eventually, the relative expressions of some significant genes were validated in the twenty external RT patients., Result: The analysis of RNA-Seq data related to RT patients with HCMV active viremia led to the identification of 140 up-regulated and 100 down-regulated DEGs. KEGG pathway analysis revealed the enrichment of DEGs in IL18 signaling, AGE-RAGE signaling pathway in diabetic complications, signaling by GPCR, Platelet activation, signaling and aggregation, Estrogen signaling pathway and signaling by Wnt due to HCMV infection. The expression levels of six genes involved in enriched pathways including F3, PTX3, ADRA2B, GNG11, GP9, HBEGF were then verified using RT-qPCR. The results were in consistent with RNA-Seq resultsoutcomes., Conclusion: This study specifies some pathobiological pathways which are activated in HCMV active infection and could be linked to the adverse indirect effects caused by HCMV infection in transplant patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Many evidence suggests that long-lasting infection can develop with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This occurrence has been widely described in immunocompromised individuals. In these patients, ineffective clearance of virus infection provides an opportunity for developing immune escape mutants. This study aimed to characterize SARS-CoV-2 intrahost evolution in five immunocompromised in comparison with five immunocompetent COVID-19 patients during treatment. We performed next-generation sequencing (NGS) on collected two oropharyngeal samples from immunocompromised and immunocompetent COVID-19 patients before and after treatment. In this study, we detected alpha and delta variants of SARS-CoV-2. The most common substitutions in structural proteins in patients with alpha variant were S-ΔY143-144, A570D, D614G and D1118H, and N-R203K and G204R, and in delta variant S-T19R, G142D, E156G, 157-158del, L452R, T478K, D614G, D950N and N-D63G, R203M and D377Y were dominant. The common variations in nonstructural and accessory proteins including nsp3-A488S, P1228L, nsp6-T77A, nsp12-P323L, G671S, nsp13-P77L, NS3-S26L, and NS7a-T120I were detected. Also some infrequent substitutions were seen in immunocompromised and immunocompetent patients. After treatment, nsp12-V166A was emerged as a remdesivir resistance and S-L452M in a patient with common variable immunodeficiency. S-E484Q was detected in a patient with acute lymphoma leukemia. This study showed the possibility of the genetic diversity and development of some new mutations in immunocompromised patients. Therefore, surveillance of these patients to characterize any new variants is necessary., (© 2023 Wiley Periodicals LLC.)

The chromogenic in situ hybridization (CISH) test is the gold standard for detecting Epstein-Barr virus (EBV)-associated gastric carcinoma (GC). Real-time (RT) PCR method is also a sensitive test that can detect the viral load in samples. As such, three EBV oncogenes were investigated in this study. RNA extraction and cDNA synthesis were performed on GC tissues of nine patients, who were previously confirmed to have EBVGC subtype. In addition, 44 patients that had positive RT-PCR but negative CISH results were also included as the control group. TaqMan RT-PCR analysis was performed to determine the expression of EBV-encoded microRNAs, and the expression of EBV-encoded dUTPase , as well as LMP2A , was analyzed by SYBR Green RT-PCR. EBV-encoded microRNAs and LMP2A were identified in 2 out of 9 (22%) EBVGC subtypes. In addition, EBV-encoded dUTPase was detected in 4 out of 9 (44.5%) EBVGC subtypes. EBV-encoded dUTPase was also expressed in a sample of the control group. The expression of LMP2A , EBV-encoded microRNAs, and EBV-encoded dUTPase viral oncogenes in patients with high EBV viral loads indicates that these expressions correlate with viral loads. Our findings indicate that the EBV-encoded dUTPase gene may have a role in EBVGC patients' non-response to treatment and might be considered a Biomarker-targeted therapy., Competing Interests: The authors declare that they have no conflict of interest.

Background: SARS-CoV-2 genomic surveillance is necessary for the detection, monitoring, and evaluation of virus variants, which can have increased transmissibility, disease severity, or other adverse effects. We sequenced 330 SARS-CoV-2 genomes during the sixth wave of the COVID pandemic in Iran and compared them with five previous waves, for identifying SARS-CoV-2 variants, the genomic behavior of the virus, and understanding its characteristics., Methods: After viral RNA extraction from clinical samples collected during the COVID-19 pandemic, next generation sequencing was performed using the Nextseq and Nanopore platforms. The sequencing data were analyzed and compared with reference sequences., Results: In Iran during the first wave, V and L clades were detected. The second wave was recognized by G, GH, and GR clades. Circulating clades during the third wave were GH and GR. In the fourth wave, GRY (alpha variant), GK (delta variant), and one GH clade (beta variant) were detected. All viruses in the fifth wave were in GK clade (delta variant). In the sixth wave, Omicron variant (GRA clade) was circulating., Conclusions: Genome sequencing, a key strategy in genomic surveillance systems, helps to detect and monitor the prevalence of SARS-CoV-2 variants, monitor the viral evolution of SARS-CoV-2, identify new variants for disease prevention, control, and treatment, and also provide information for and conduct public health measures in this area. With this system, Iran could be ready for surveillance of other respiratory virus diseases besides influenza and SARS-CoV-2., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are common viruses that continuously circulate in the human population. Previous studies showed the circulation of HCoVs during the cold months in Iran. We studied the circulation of HCoVs during coronavirus disease 2019 (COVID-19) pandemic to find the impact of pandemic on the circulation of these viruses., Methods: As a cross-sectional survey conducted during 2021 to 2022, of all throat swabs sent to Iran National Influenza Center from patients with severe acute respiratory infection, 590 samples were selected to test for HCoVs using one-step real-time RT-PCR., Results: Overall, 28 out of 590 (4.7%) tested samples were found to be positive for at least one HCoVs. HCoV-OC43 was the most common (14/590 or 2.4%), followed by HCoV-HKU1 (12/590 or 2%) and HCoV-229E (4/590 or 0.6%), while HCoV-NL63 was not detected. HCoVs were detected in patients of all ages and throughout the study period with peaks in the cold months of the year., Conclusions: Our multicenter survey provides insight into the low circulation of HCoVs during the COVID-19 pandemic in Iran in 2021/2022. Hygiene habits and social distancing measures might have important role in decreasing of HCoVs transmission. We believe that surveillance studies are needed to track the pattern of HCoVs distributions and detect changes in the epidemiology of such viruses to set out strategies in order to timely control the future outbreaks of HCoVs throughout the nation., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Skin rash is one of the most common complications during childhood. Viral agents play an essential role in the development of such symptoms. Present study aims to determine the prevalence and genetic variability of Human Herpesvirus 6 and 7 (HHV-6 and HHV-7) infections and their subtypes in children under 5 years of age with skin rash and negative for rubella and measles. We used serum and throat swap samples from 196 children with skin rash and fever. ELISA and IFA tests were performed to detect antibodies against HHV6/7. Sequencing was performed using Sanger sequencing, and BioEdit and MEGA10 software were used for sequence analysis. According to the results, 66% and 40% of cases were positive for HHV-6 IgM and HHV-7 IgM, respectively. According to the molecular analysis, HHV-6 Nested-PCR was positive in 18% of cases, however, HHV-7 Nested-PCR was positive in 7.7% of cases. On the other hand, HHV-6 IgG and HHV-7 IgG were positive in 91% and 55% of study cases, respectively. For HHV-6, we found some genetic variabilities resulting in antigenic changes compared to reference strains. HHV-7 isolates showed no genetic differentiation and had a stable gene sequence. Based on the results, the detection of some cases of HHV6/7 primary infection and the presence of specific symptoms of roseola in the study population needs continuous evaluation of HHV6/7 frequency and distribution, also genetic variabilities of HHV6. This can pave the way for investigating HHV6 immune evasion and vaccine research and studying the relationship between viral genetic variations and other factors like disease severity. Furthermore, it is necessary to determine the relation between HHV6 genetic changes and latent infection to be considered in possible future vaccines and antiviral drug development., (© 2023 Wiley Periodicals LLC.)

SARS-COV-2 is responsible for the current worldwide pandemic, which started on December 2019 in Wuhan, China. On March 2020 World Health Organization announced COVID-19 as the new pandemic. Some SARS-COV-2 variants have increased transmissibility, cause more severe disease (e.g., increased hospitalizations or deaths), are resistant to antibodies produced by the previous infection or vaccination, and there is more difficulty in treatment and diagnosis of them. World Health Organization considered them as SARS-CoV-2 variants of concern. The introductory reproduction rate (R 0 ) is an epidemiologic index of the transmissibility of the virus, defined as the average number of persons infected by the virus after known contact with an infectious person in a susceptible population. An R 0  > 1 means that the virus is spreading exponentially, and R 0  < 1, means that the outbreak is subsiding. In various studies, the estimated R and VOC growth rates were reported to be greater than the ancestral strains. However, it was also a low level of concordance between the estimated Rt of the same variant in different studies. It is because the R of a variant not only dependent on the biological and intrinsic factors of the virus but also several parameters can affect the R0, including the duration of contagiousness and the likelihood of infection per contact. Evaluation of changes in SARS-CoV-2 has shown that the rate of human-to-human transmission of this virus has increased. Like other viruses with non-human sources which succeeded in surviving in the human population, SARS-CoV-2 has gradually adapted to the human population, and its ability to transmit from human to human has increased. Of course, due to the continuous changes in this virus, it is crucial to survey the rate of transmission of the virus over time., (© 2023. The Author(s).)

Background and Objectives: Human rhinoviruses (HRVs) and human adenoviruses (HAdVs) are among the most prevalent viruses in hospitalized patients with severe acute respiratory infection (SARI). This study aimed to evaluate the molecular characterization of HRV and HAdV in hospitalized patients with SARI, who aged ≤ 18 years in Tehran, Iran., Materials and Methods: To detect these two viruses, a conventional nested RT-PCR (Reverse transcription-polymerase chain reaction) assay was performed on 264 throat swabs collected from December 2018 to March 2019. The epidemiological data were analyzed and phylogenetic trees were constructed., Results: Of 264 cases with SARI, 36 (13.6%) and 28 (10.6%) were positive for HAdV and HRV respectively. Of 21 HRV sequenced samples, HRV-A (42.9%), HRV-B (9.5%) and HRV-C (47.6%) and of 36 HAdV sequenced samples, HAdV-C6 (38.9%), HAdV-B7 (22.2%), HAdV-B3 (11.1%), HAdV-B16 (5.6%), HAdV-C5 (13.9%), HAdV-C57 (5.6%), HAdV-E4 (2.8%); were detected in children with SARI. Some viral genotypes appeared to cause more severe disease, which may lead to hospitalization., Conclusion: Large-scale studies are recommended to investigate the epidemiology and molecular characterizations through surveillance networks to provide useful information on etiology, seasonality, and demographic associations in patients with SARI., (Copyright © 2023 The Authors. Published by Tehran University of Medical Sciences.)

Introduction: Human cytomegalovirus (HCMV) infection is one of the most common viral complications in kidney transplant recipients. Although there are effective treatments strategies for the HCMV infection, this infection is still one of the causes of kidney transplant rejection., Methods: A total of 246 kidney transplant recipients participated in this cross-sectional study. Viral DNA was extracted from these plasma samples, and the presence of HCMV genome was determined by semi-nested PCR with specific primers for the HCMV B glycoprotein gene. Sanger sequencing analyses were carried out to determine HCMV genotypes, and the Mega x software was used for nucleotide alignment and construction of a phylogenetic tree., Results: HCMV DNA was detected in 11 (4.47%) recipients. According to the phylogenetic analysis, HCMV gB3 was 50% among kidney transplant recipients, followed by gB4 30% and gB1 20%; however, the gB2 genotype was not detected., Conclusions: This study demonstrated that the HCMV infection in our patients is relatively low because all transplant recipients received appropriate prophylaxis, thereby antiviral prophylaxis is recommended for all patients at risk of HCMV infection after kidney transplantation. Also, gB3 was the most predominant genotype among our kidney transplant recipients that was related to the higher rate of prevalence of severe HCMV infections. Moreover, an elevated serum creatinine level was detected in patients at the time of detection of HCMV infection., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Human adenovirus (HAdV) is an important viral agent in children which can lead to severe acute respiratory infection (SARI). Reports on molecular epidemiology of HAdVs in Iran are limited. This case-control study is conducted to compare the HAdV infection rate and molecular epidemiology among two groups of children with and without respiratory symptoms in Tehran, Iran during 2018-2019., Methods: Nested PCR was performed on 120 oropharyngeal swabs taken from children aged five and younger with SARI who were hospitalized as the case group, and 120 oropharyngeal swabs were collected from children of the same age without respiratory symptoms as the control group. For positive samples Sanger sequencing was done and a phylogenetic tree was drawn afterward., Results: Out of 120 cases, 8 (6.6%) tested positive for eachHAdV types including 6 (75%) HAdV-B7, 1 (12.5%) HAdV-C2, and 1 (12.5%) HAdV-C6. Among the control group, out of 120 samples, 8 (6.6%) were positive comprising 5 (62.5%) HAdV-C5, 2 (25%) HAdV-F41, and 1 (12.5%) HAdV-C6., Conclusion: The present study indicated a different viewpoint of HAdV molecular epidemiology in which the genotypes were compared in children with and without respiratory symptoms. HAdV prevalence was equally common in cases and controls but different genotypes were detected in these two groups. HAdV-B7 was the main type among children with SARI, dissimilar to children with no respiratory symptoms where HAdV-C5 was the predominant type. Detecting HAdV-F in oropharyngeal swabs was a rare finding, which requires further investigation., (© 2022. The Author(s).)

Background and Objectives: Neuraminidase inhibitors (NAIs) as an imperative antiviral for influenza prophylaxis and treatment are being consumed worldwide. Increasing use of these antivirals might be associated with drug resistance. Regarding the significance of these variations, this study aimed to investigate the mutations occurring in the NA gene of influenza A viruses leading to oseltamivir resistance during 2017-2019 in Iran., Materials and Methods: In this cross-sectional study, 40 influenza A (H1N1, H3N2) strains, isolated in National Influenza Center (NIC) from patients with Severe Acute Respiratory Infection (SARI) during 2017-2019 were subjected to RT-PCR and sequencing of NA complete gene. The frequency of oseltamivir resistance and variation of NA amino acids in these strains were investigated., Results: No significant mutation conferring oseltamivir resistance was detected. However, NA antigenic sites in these strains depicted minor changes compared to the vaccine strains. Among H3N2 isolates, mutations at 329, 344, 346 and 385 and among H1N1 isolates mutations at 143 and 188 residues occurred in NA antigenic regions., Conclusion: Evaluation of NA gene sequences, showed no resistant viruses to oseltamivir. Given that the viruses in the present study were the last viruses circulating in Iran before COVID-19 pandemic, the results will be beneficial to have a worthy comparison with the strains circulating after the pandemic. Constant monitoring for the emergence of drug-resistant variants and antigenic changes are crucial for all countries., (Copyright © 2022 The Authors. Published by Tehran University of Medical Sciences.)

Background and Objectives: Parvovirus B19 (B19V) is usually transmitted through respiratory tract, but can also be received through blood transfusion. This study evaluated the seroprevalence, DNA existence, and circulating genotypes of B19V in hemophilia patients., Materials and Methods: Serum samples of cases and controls were analyzed for B19V using ELISA and real-time PCR. Finally, obtained sequences were used for genotyping., Results: Among cases, 3% were anti-B19V IgM positive and 47% were anti-B19V IgG positive and B19V DNA was detected in 16% of them. However, among controls, 38% were anti-B19V IgG positive (P>0.05) and 5% were B19V DNA positive (P= 0.019). Also ∼13% of cases were positive and all of controls were negative for IgG avidity test (P= 0.029). Viral load in case group was higher than control group (P = 0.037)., Conclusion: Since hemophilia patients receive large amounts of blood factors, prevalence of B19V in these patients might be higher than normal subjects., (Copyright © 2022 The Authors. Published by Tehran University of Medical Sciences.)

Acute respiratory infections (ARIs) are one of the leading causes of illness and death among community members worldwide. Viral infections are the most common agents estimated to be involved in these patients. This study aimed to investigate the prevalence of human respiratory syncytial virus (hRSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among children with ARIs. This study evaluated the presence of SARS-CoV-2 and hRSV in 168 throat and nasopharyngeal swab samples using real-time RT-PCR. All samples were collected from children under 5 years old with ARIs who attended Children's Medical Center, Tehran, Iran, and sent to the Iranian National Influenza Center with appropriate conditions in 2021. Chi-square and Fisher's exact tests were used for comparison of the data of the prevalence of hRSV and SARS-CoV-2 infections among children. Of 168 patients examined, 95 (57%) were male and 73 (43%) female. Out of them, 47 (28%) cases were younger than 1 year old and 121 cases (72%) were 1-5 years old. The most common clinical manifestations of patients were cough (78%), nausea (31%), diarrhea (27%), and fever (18%). Among 168 patients, no hRSV was detected, while the SARS-CoV-2 genome was identified in 16 (9.5%) patients. Among 16 positive cases of SARS-CoV-2, 8 (50%) were under 1 year old and 8 positive cases were 1-5 years old. This study was performed at cold months of the year but due to the coronavirus disease 2019 pandemic and adherence to health protocols, school closures, and virtual classes, no cases of hRSV infections were identified., (© 2022 Wiley Periodicals LLC.)

Depression is one of the most important causes of disability and loss of useful life of people around the world. Acute respiratory infection caused a large number of severe illnesses and deaths of the world and most of these due to viral infections, which is estimated more than 80% of respiratory infections. Detection of viruses by immune pathogen recognition receptors activates the intracellular signaling cascade and eventually cause produces interferons. Inflammatory process begins with secretion of interferons and the expression of interferon-stimulated genes. One of the most important of these genes is indoleamine-pyrrole 2,3-dioxygenase (IDO), which plays a major role in tryptophan catabolism. IDO is an intracellular monomeric enzyme that is also responsible for breaking down and consuming tryptophan in the Kynurenine pathway. Increased inflammation has been linked to decrease tryptophan concentrations and increase kynurenine levels. We tried to explain the role of inflammation by viral respiratory infections in causing depression.

Purpose: Whole genome sequencing of SARS-CoV2 is important to find useful information about the viral lineages, variants of interests and variants of concern. As there are not enough data about the circulating SARS-CoV2 variants in Iran, we sequenced 54 SARS-CoV2 genomes during the 5 waves of pandemic in Iran., Methods: After viral RNA extraction from clinical samples collected during the COVID-19 pandemic, next generation sequencing was performed using the Nextseq platform. The sequencing data were analyzed and compared with reference sequences., Results: During the 1st wave, V and L clades were detected. The second wave was recognized by G, GH and GR clades. Circulating clades during the 3rd wave were GH and GR. In the fourth wave GRY (alpha variant), GK (delta variant) and one GH clade (beta variant) were detected. All viruses in the fifth wave were in clade GK (delta variant). There were different mutations in all parts of the genomes but Spike-D614G, NSP12-P323L, N-R203K and N-G204R were the most frequent mutants in these studied viruses., Conclusions: These findings display the significance of SARS-CoV2 monitoring to help on time detection of possible variants for pandemic control and vaccination plans., Competing Interests: The authors have declared that no competing interests exist.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country., (© 2021 Wiley-VCH GmbH.)