The molecular footprints of BK virus in the product of conception over the second and third gestational trimesters.

OBJECTIVE: Prior studies have shown controversial results on the vertical transmission of BK virus (BKV). The present study aimed to assess the possibility of BKV vertical transmission from mother to fetus in the product of conception (embryo, fetuses, and/or placentas) over the three stages of pregnancy. RESULTS: Of the 26 placental studied tissues, 6 were in the first trimester, and none of which were positive. Only one out of the 13 (7.7%) placental materials in the second trimester was positive. Only one out of 7 (14%) placental materials of the third trimester was positive. There were cases that no virus was detected in their placental but BKV was detected in their other tissues. Among 26 conceptuses, 17 (65%) were negative for BKV and 9 (34.6%) were positive, 7/13 (54%) were positive in the second, and 2/7 (29%) were positive in the third trimester fetuses. BKV was most frequently detected in the liver (eight cases), heart (three cases), and placenta (2 cases). There were cases that no virus was detected in their placental but BKV was detected in their other tissues.

In vitro evaluation of antiviral activity of Shouchella clausii probiotic strain and bacterial supernatant against herpes simplex virus type 1.

Herpes simplex virus-1 (HSV-1) is an important human neurotropic virus infecting 70% of the world population. Due to the emergence of viral resistance via mutations in HSV-1 genes and some of the adverse effects of antiviral compounds, there is a growing need for safe, novel, and effective therapeutic and preventive strategies. The aim of the present study was to investigate for the first time the potential antiviral activity of Shouchella clausii probiotic strain and bacterial supernatant against HSV-1. The MTT assay was used to determine the possible cytotoxicity of the S. clausii and bacterial supernatant. Vero cells were treated by S. clausii, bacterial supernatant, and HSV-1 under pre-treatment (incubation of Vero cells with S. clausii then HSV-1 inoculation), pre-incubation (mixture of co-incubated HSV-1/S. clausii added to Vero cell), competition (adding HSV-1 and S. clausii into Vero cells simultaneously) and post-treatment (Vero cells inoculated with HSV-1 then incubated with S. clausii) assays. Viral titer reduction (TCID50) and viral DNA relative quantification by real-time PCR were measured in each experimental condition. The results indicated that S. clausii and its supernatant had the greatest inhibitory activity toward HSV-1 in pre-treatment assay. The HSV-1 titer treated with S. clausii, and bacterial supernatant was 3.6 and 2.2 Log10TCID50/mL lower compared to the control (7.66 Log10TCID50/mL). Results showed an antiviral effect of S. clausii and its supernatant. S. clausii could be considered as a novel inhibitor for HSV-1 infection.

The Persistence Time of SARS-CoV-2 RNA in Hospitalized COVID-19 Patients: A Prospective Study.

BACKGROUND: In late December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), spread to almost all countries worldwide. The outbreak of this virus has been confirmed on 19th February, 2020, in Iran. OBJECTIVE: The aim of this study was to investigate the time of viral RNA clearance in swab and serum samples of COVID-19 patients having received different medications. We also evaluated different factors that may affect viral RNA persistence in patients infected by SARS-CoV-2. METHODS: In March 2020, twenty-one hospitalized COVID-19 patients participated in this prospective study. All patients received antiviral agents in their routine care. Throat swabs and blood samples were obtained from all patients in different intervals, including day 3 or 5, day 7, day 10, and finally, 14 days after the first positive real-time RT-PCR (rRT-PCT) test. RESULTS: The median time from the symptom onset (SO) to the first negative rRT-PCR results for throat swabs and serum samples of COVID-19 patients was 18 and 14 days, respectively. These times were more significant in patients with lymphopenia, oxygen saturation ≤ 90%, and comorbidity. CONCLUSION: This preliminary study highlights that SASR-CoV-2 RNA was not detectable in the upper respiratory tract for longer than three weeks. In addition, SARS-CoV-2 may persist for a long period of time in the respiratory than in the serum samples. This study supports the idea that in limited resource settings, the patients should be tested earlier than three weeks for discharge management.

Understanding the pivotal roles of ACE2 in SARS-CoV-2 infection: from structure/function to therapeutic implication.

In December 2019, a novel respiratory tract infection, from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in China that rapidly spread around the world. This virus possesses spike (S) glycoproteins on the surface of mature virions, like other members of coronaviridae. The S glycoprotein is a crucial viral protein for binding, fusion, and entry into the target cells. Binding the receptor-binding domain (RBD) of S protein to angiotensin-converting enzyme 2 (ACE 2), a cell-surface receptor, mediates virus entry into cells; thus, understanding the basics of ACE2 and S protein, their interactions, and ACE2 targeting could be a potent priority for inhibition of virus infection. This review presents current knowledge of the SARS-CoV-2 basics and entry mechanism, structure and organ distribution of ACE2, and also its function in SARS-CoV-2 entry and pathogenesis. Furthermore, it highlights ACE2 targeting by recombinant ACE2 (rACE2), ACE2 activators, ACE inhibitor, and angiotensin II (Ang II) receptor blocker to control the SARS-CoV-2 infection.

SARS-CoV-2: an imperative maternal-fetal concern.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a newly emerged virus which belongs to Coronaviridae family within the betacoronavirus genus. Previous reports demonstrated that other betacoronaviruses were responsible for adverse outcomes during pregnancy in human. Due to inadequate data, the consequences of a SARS-CoV-2 infection during pregnancy is still a public health concern in the second year of SARS-CoV-2 circulation in human population. Herein, we aimed to review the probable risk of intrauterine vertical transmission of SARS-CoV-2 infection to the fetus, its adverse outcomes during pregnancy for both mother and the fetus and maternal risk factors which affect the severity Coronavirus disease 2019 (COVID-19.

Prevalence of Human Metapneumovirus Infections in Iran: A Systematic Review and Meta-Analysis.

BackgroundWe sought to systematically review the literature and perform a meta-analysis by assessing the prevalence of human metapneumovirus (hMPV) infections from a number of studies conducted in Iran. Methods: Entire studies addressing epidemiology of hMPV in Iran using data from PubMed, Scopus, Science Direct, Web of science, Google Scholar, Embase, and national Persian databases up to June 2019 were included. Results: The estimated prevalence of hMPV was 8.9% (95% CI 5.4-14.2) in different regions in Iran. Compared to the global rate, in Iran hMPV infection presented an intermediate prevalence rate. The majority of hMPV positive patients were pediatric populations with pooled prevalence of 7.6% (I2 = 95%, 95% CI 3.5-15.6). Conclusion: This first comprehensive review covering researches over the last 11 years expanded our knowledge about hMPV circulating in Iran. Future large epidemiological studies are needed for the evaluation of hMPV prevalence and genotype distribution in different unanalyzed regions in Iran.

Molecular characterization of the glycoprotein and fusion protein in human respiratory syncytial virus subgroup A: Emergence of ON-1 genotype in Iran.

HRSV is a principle cause of infant hospitalization, childhood wheezing and a common pathogen in the elderly. Limited information exists regarding HRSV genotypes in Iran. In order to better understand HRSV strain diversity, we performed an in-depth evaluation of the genetic variability of the HRSV F protein detected in children under two years of age that, presented with acute respiratory symptoms during 2015-2016 in Tehran. A total of 180 nasopharyngeal swabs were evaluated. The HRSV positive samples were genotyped for G and F gene sequences using RT-PCR and sequencing methods. Phylogenetic analysis was performed using the neighbor-joining and maximum likelihood methods. Genetic and antigenic characteristics of the F gene, nucleotide and amino acids in significant positions and immune system binding regions, as well as the p-distance, positive/negative selection site, linear epitopes and glycosylation sites were investigated in all selected sequences. Among the 83 HRSV positive samples, the Fifty-five cases were successfully sequenced. All of them were classified as subgroup A and belonged to the ON-1 genotype, which possessed 72-nt duplication in the G gene. This study is the first report on the emergence of ON-1 in Iran. ON-1 Iranian sequences clustered in three lineages according to virus fusion (F) gene variations. F gene sequence analysis showed that all genetic changes in the isolates from Iran were base substitutions and no deletion/insertions were identified. The low dN/dS ratio and lack of positively selected sites showed that the fusion genes found in the strains from Iran are not under host selective pressure. Continuing and long-term molecular epidemiological surveys for early detection of circulating and newly emerging genotypes are necessary to gain a better understanding of their epidemic potential.

Molecular Detection of Adeno-Associated Virus DNA in Cases of Spontaneous and Therapeutic Abortion.

BACKGROUND: Adeno-associated viruses (AAVs) have been found in human blood cells, cervical biopsies, and epithelial cell brushings, endometrium, and abortion material, which suggest their possible roles in the induction of miscarriage. OBJECTIVE: In this case control study, the presence of AAV DNA in placental tissue of spontaneous and therapeutic abortions was compared. METHOD: Placenta samples were evaluated for AAV DNA by hemi-nested PCR in miscarriages occurring in the first 24 weeks of pregnancy from therapeutic and spontaneous abortions. RESULTS: Eighty-one therapeutic abortions (control group) and 83 spontaneous abortions (case group) were evaluated. Sixty-two (38.2%) of 164 abortions were AAV positive, including 35 (21.6%) spontaneous abortions and 27 (16.6%) therapeutic abortions. CONCLUSION: There was no statistically significant difference between the presence of the AAV genome in spontaneous and therapeutic abortions. This observation was consistent with other studies in this area.

Prevalence of adeno-associated virus and human papillomavirus DNA in Iranian women with and without cervical cancer.

There is plenty of substantial evidence to support anti-tumor activity of viruses. Adeno-associated virus (AAV) may interact with human papillomavirus (HPV) to modify the risk of cervical neoplasia. The seroprevalence of AAV among women with cervical cancer has been reported to be lower than healthy ones. In spite of this finding, detection of AAV DNA in cervical biopsies does not entirely support the inverse association between AAV seropositivity and cervical cancer. This association is still controversial and requires more thorough evaluation in different countries. The aim of this case-control study was to find the prevalence of AAV and HPV DNA sequences in Iranian women with and without cervical cancer to assess the probable association of AAV infection and cervical cancer. In this study, paraffin-embedded tissue samples of 61 cervical cancer cases and 50 healthy controls (HCs) were investigated for AAV and HPV DNA by semi-nested and nested PCRs respectively. AAV DNA was detected in 7 cases (14%) of HCs and 9 specimens (14.8%) of case group. According to the branching in the phylogenetic tree, AAV2 was the only type detected in this study. Moreover, HPV DNA was detected in 8 cases (16%) of HCs and 44 specimens (72.13%) of case group. In conclusion, a low proportion of cervical biopsies from Iranian women contained AAV-2 genome. No significant difference in correlation between HPV and cervical cancer in presence or absence of AAV genome in cervix was found.

Inhibition of Respiratory Syncytial Virus Replication by Simultaneous Targeting of mRNA and Genomic RNA Using Dual-Targeting siRNAs.

We attempted to generate siRNAs with two active strands, which can simultaneously knock down the expression of mRNA and viral genomic RNA. In this study, short hairpin RNAs (shRNAs) against N and F genes were used. Expression of F and N mRNA transcripts as well as genomic RNA was determined with relative real-time RT-PCR. The RSV load in infected cell culture supernatant was determined by absolute quantitative real-time PCR. We found that (i) in the presence of shRNA-N, a greater reduction in viral genomic RNA was found; (ii) the level of expression at MOI 0.01 was reduced more than MOI 0.1; (iii) reduction in N transcript was greater than F; and (iv) finally, in combination pre-treatment with two shRNAs, the reduction was not significant as compared to single shRNA transfection. shRNAs also inhibited the production of RSV progeny as shown by viral load in infected HEp-2 cells. (i) Virus load reduction was greater at MOI 0.01 than 0.1 and (ii) significant load reduction was not seen with combination shRNA pre-treatment. The antiviral potency was also confirmed by plaque assay and western blot analysis. Our results provided further evidence that RNAi could be a powerful treatment option against respiratory viruses.

Molecular detection of respiratory viruses in clinical specimens from children with acute respiratory disease in Iran.

BACKGROUND: Viruses are the most common causes of respiratory tract infections in children. The implementation of rapid virology assays can identify the most common pathogens involved. This study was undertaken on Iranian children less than 6 years old with respiratory infection. METHODS: A total of 202 specimens were tested for the presence of 9 respiratory viruses by developing 3 multiplex reverse transcription-polymerase chain reaction and 1 uniplex polymerase chain reaction assays. RESULTS: Viral pathogens were detected in 92 samples (45.5%) with 5.4% having dual infections. Overall, respiratory syncytial virus was the most frequently identified virus (16.8%), followed by adenovirus (14.4%), influenza A virus (4.9%), parainfluenza virus-3 (4.4%), parainfluenza virus-1 (2.9%), and both influenza B virus and hMPV (0.49). CONCLUSIONS: Respiratory tract infection is a frequent cause of pediatric morbidity and mortality and a common reason for admission in acute care hospitals and outpatients visits. Appropriate diagnostic testing is important for specific diagnosis at an early stage of the illness because of the similarity in clinical presentation of patients with different viral infections caused by several respiratory pathogens.