Prevalence of enteric adenovirus and co-infection with rotavirus in children under 15 years of age with gastroenteritis in Qom, Iran.

Aim: The current study is the first performed in Qom to determine the prevalence of adenovirus and co-infections with rotavirus in children aged <15 years with gastroenteritis symptoms. Background: Gastroenteritis-associated viral infections are a cause of death among young children worldwide, especially in developing countries. The Adenovirus species F (40 and 41) are responsible for a range of acute diarrhea cases among infants and children. Methods: Over a period of 9 months, a total of 130 children suffering from intestinal problems who referred to the infectious ward of Children's Hospital were enrolled in the current study. After clinical examination and collection of demographic information, fecal samples were obtained from the patients. Viral genomes were extracted with a commercial kit and amplified and typed by adenovirus-specific PCR assay. Adenovirus-positive samples were also evaluated for co-infection with rotavirus. Results: Patients had a mean±SD age of 2.66±2.72 years; 63.1% of patients were male and 36.9% were female. Adenovirus infection was identified in 23 cases (17.7%), 21 (91.0%) and 2 (9.0%) of which were type 41 and type 40, respectively. Fever was the most common clinical manifestation among adenovirus-positive patients. No significant difference was observed between adenovirus infection and clinical symptoms, seasonal pattern, or serum laboratory results. Co-infection was found in only 5 cases (21.7%). Conclusion: This study was the first to demonstrate adenovirus infection with a relatively high prevalence among children, especially infants, in Qom. The findings further revealed co-infection with rotavirus, indicating a health problem in this region.

Co-administration of rotavirus nanospheres VP6 and NSP4 proteins enhanced the anti-NSP4 humoral responses in immunized mice.

Inconveniences associated with the efficacy and safety of the World Health Organization (WHO) approved/prequalified live attenuated rotavirus (RV) vaccines, sounded for finding alternative non-replicating modals and proper RV antigens (Ags). Herein, we report the development of a RV candidate vaccine based on the combination of RV VP6 nanospheres (S) and NSP4112-175 proteins (VP6S + NSP4). Self-assembled VP6S protein was produced in insect cells. Analyses by western blotting and transmission electron microscopy (TEM) indicated expression of VP6 trimer structures with sizes of ≥140 kDa and presence of VP6S. Four group of mice were immunized (2-dose formulation) intra-peritoneally (IP) by either¨VP6S + NSP4¨ or each protein alone (VP6S or NSP4112-175) emulsified in aluminium hydroxide or control. Results indicated that VP6S + NSP4 formulation induced significant anti-VP6 IgG (P < 0.001) and IgA (P < 0.05) as well as anti-NSP4 IgG (P < 0.001) and enhancement of protective immunity. Analyses of anti-VP6S and anti-NSP4 IgG subclass (IgG1 and IgG2a) showed IgG1/IgG2a ≥6 and IgG1/IgG2a ≥3 ratios, respectively indicating Th2 polarization of immune responses. The combination of VP6S + NSP4 proteins emulsified in aluminum hydroxide adjuvant might present a dual universal, efficient and cost-effective candidate vaccine against RV infection.

Association between serum inflammatory parameters and the disease severity in COVID-19 patients.

OBJECTIVE: Most patients infected with the novel coronavirus (SARS-CoV-2), as the causative agent of COVID-19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID-19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity. METHODS: In this prospective cross-sectional study, 50 patients with COVID-19 and 20 patients without COVID-19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non-severe and severe. Differences in the serum levels of C-reactive protein (CRP), IL-6, and TNF-α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed. RESULTS: Out of the 50 patients with COVID-19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID-19 patients in terms of gender and age. Blood tests of COVID-19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL-6, TNF-α, and CRP between the severe and non-severe groups, which were higher in the severe group. Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL-6 (r = 0.74), LYM with NEU (r = -0.97), and ESR with TNF-α (r = 0.7). CONCLUSION: The findings of this study, as the first study in Iran, suggest that the levels of IL-6, TNF-α, ESR, and CRP could be used to predict the severity of COVID-19 disease.

Severe acute respiratory syndrome-coronavirus-2 spike (S) protein based vaccine candidates: State of the art and future prospects.

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which is responsible for a global pandemic that started in late 2019 in Wuhan, China. To prevent the worldwide spread of this highly pathogenic virus, development of an effective and safe vaccine is urgently needed. The SARS-CoV-2 and SARS-CoV share a high degree of genetic and pathologic identity and share safety and immune-enhancement concerns regarding vaccine development. Prior animal studies with first generation (whole virus-based) preparations of SARS-CoV vaccines (inactivated and attenuated vaccine modalities) indicated the possibility of increased infectivity or eosinophilic infiltration by immunization. Therefore, development of second and third generation safer vaccines (by using modern vaccine platforms) is actively sought for this viral infection. The spike (S) protein of SARS-CoVs is the main determinant of cell entry and tropism and is responsible for facilitating zoonosis into humans and sustained person-to-person transmission. Furthermore, 'S' protein contains multiple neutralizing epitopes that play an essential role in the induction of neutralizing antibodies (nAbs) and protective immunity. Moreover, T-cell responses against the SARS-CoV-2 'S' protein have also been characterized that correlate to the IgG and IgA antibody titres in Covid-19 patients. Thus, S protein is an obvious candidate antigen for inclusion into vaccine platforms against SARS-CoV-2 viral infection. This manuscript reviews different characteristics of S protein, its potency and 'state of the art' of the vaccine development strategies and platforms using this antigen, for construction of a safe and effective SARS-CoV-2 vaccine.

High viral load detection of human Cosavirus in Iranian pediatric patients with acute gastroenteritis.

AIM: The present study implemented an RT-qPCR assay for the detection and quantification of human cosavirus in stool specimens from pediatric patients involved in acute gastroenteritis. BACKGROUND: Human cosavirus is a newly recognized virus that seems to be partly related to acute gastroenteritis in pediatric patients. However, the relationship between human cosavirus and diseases in humans is unclear. METHODS: From January 2018 to December 2019, a total of 160 stool samples were collected from pediatric patients presenting with acute gastroenteritis in a hospital in Karaj, Iran. After viral RNA extraction, RT-qPCR was performed to amplify the 5'UTR region of the human cosavirus genome and viral load was analyzed. RESULTS: The human cosavirus genomic RNA was detected in 4/160 (2.5%) stool samples tested. The maximum viral load was determined to be 4.6×106 copies/ml in one sample obtained from a 4-year-old patient. CONCLUSION: The human cosavirus as a new member of the Picornaviridae family was illustrated in fecal samples from pediatric patients with acute gastroenteritis in Iran. This is the first documentation of human cosavirus circulation in Iranian children.

Discovery of Novel Pyruvate Kinase Inhibitors Against Leishmania major Among FDA Approved Drugs Through System Biology and Molecular Docking Approach.

OBJECTIVES: Leishmaniasis is one of the common forms of neglected parasitic diseases that cause a worldwide disease burden without any effective therapeutic strategy. Control of the disease currently relies on chemotherapy because most of the available drugs have toxic side-effects and drug-resistant strains have emerged. Therefore, the development of new therapeutic strategies to treat patients for leishmaniasis has become a priority. The first step in drug discovery is to identify an effective drug target by methods such as system biology. Protein kinases are a promising drug target for different diseases. Due to lack of a functional krebs cycle in Leishmania species, they use glycolysis as the only source of ATP generation. Pyruvate kinase is the enzyme involved in the last step of glycolysis and considered as essential enzyme for the Leishmania survival. MATERIALS AND METHODS: This study sought to discover FDA approved compounds against the leishmanial pyruvate kinase protein. Our approach involved using quantitative proteomics, protein interaction networks and docking to detect new drug targets and potent inhibitors. RESULTS: Pyruvate kinase was determined as the potential drug target based on protein network analysis. The docking studies suggested trametinib and irinotecan with high binding energies of -10.4 and -10.3 kcal/mol, respectively, as the potential chemotherapeutic agents against L. major. CONCLUSION: This study demonstrated the importance of integrating protein network analysis and molecular docking to identify new anti-leishmanial drugs. These potential inhibitors constitute novel drug candidates that should be tested in vitro and in vivo to determine their potential as an alternative chemotherapy in the treatment of leishmaniasis.

Computation screening and molecular docking of FDA approved viral protease inhibitors as a potential drug against COVID-19.

AIM: This study demonstrated potent inhibitors against COVID-19 using the molecular docking approach of FDA approved viral antiprotease drugs. BACKGROUND: COVID-19 has now spread throughout world. There is a serious need to find potential therapeutic agents. The 3C-like protease (Mpro/6LU7) is an attractive molecular target for rational anti-CoV drugs. METHODS: The tertiary structure of COVID-19 Mpro was obtained from a protein data bank repository, and molecular docking screening was performed by Molegro Virtual Docker, ver. 6, with a grid resolution of 0.30 Å. Docking scores (DOS) are representative of calculated ligand-receptor (protein) interaction energy; therefore, more negative scores mean better binding tendency. Another docking study was then applied on each of the selected drugs with the best ligands separately and using a more accurate RMSD algorithm. RESULTS: The docking of COVID-19 major protease (6LU7) with 17 selected drugs resulted in four FDA approved viral antiprotease drugs (Temoporfin, Simeprevir, Cobicistat, Ritonavir) showing the best docking scores. Among these 4 compounds, Temoporfin exhibited the best DOS (-202.88) and the best screened ligand with COVID-19 Mpro, followed by Simeprevir (-201.66), Cobicistat (-187.75), and Ritonavir (-186.66). As the best screened ligand, Temoporfin could target the Mpro with 20 different conformations, while Simeprevir, Cobicistat, and Ritonavir make 14, 10, and 10 potential conformations at the binding site, respectively. CONCLUSION: The findings showed that the four selected FDA approved drugs can be potent inhibitors against COVID-19; among them, Temoporfin may be more potent for the treatment of the disease. Based on the findings, it is recommended that in-vitro and in-vivo evaluations be conducted to determine the effectiveness of these drugs against COVID-19.

Neutrophil to lymphocyte ratio and C-reactive protein level as prognostic markers in mild versus severe COVID-19 patients.

AIM: This research aimed to investigate neutrophil-to-lymphocyte ratio (NLR) with C-reactive protein to identify potential clinical predictors and analyze differences among severe and non-severe COVID-19 patients. BACKGROUND: NLR and CRP are established markers that reflect systemic inflammatory, and these parameters alter in patients with novel coronavirus (SARS-CoV-2) pneumonia (COVID-19). METHODS: A population of patients with COVID-19 referred to Loghman Hospital in Tehran was analyzed. The baseline data of laboratory examinations, including NLR and CRP levels, was collected. Pearson analysis was used to assess the independent relationship between the NLR with disease severity and CRP levels. RESULTS: COVID-19 cases comprised 14 (20%) patients with severe disease and 56 (80%) with non-severe infection. The mean values of WBC, NEU, LYM, and NLR of the severe patients were significantly higher than those of the non-severe patients. Forty-six patients (65.7%) had NLR >1, and the remaining patients had NLR <1. Plasma CRP levels were higher in severe cases than in non-severe cases, and this difference was significant. The results showed that NLR was positively correlated with CRP levels (R=0.23) and negatively correlated with WBC (R=-0.38). CRP (AUC = 0.97, 95% CI: 0.95-0.99) and NLR (AUC = 0.87, 95% CI: 0.81-0.93) had very good accuracy in predicting the severity of COVID-19 disease. CONCLUSION: The findings of this study indicated that the integration of NLR and CRP may lead to improved predictions and is recommended as a valuable early marker to assess prognosis and evaluate the severity of clinical symptoms in COVID-19 patients.

Distribution of Human Papillomavirus and Antisperm Antibody in Semen and Its Association with Semen Parameters Among Infertile Men.

BACKGROUND: Sexually transmitted infections (STIs) can be associated with infertility. Human papillomavirus (HPV) has been identified as a potential agent in male infertility. Also, anti-sperm antibodies (ASA) have been detected in men with infertility. The aim of this study was to investigate the prevalence and association of HPV and ASA in infected semen of infertile men. METHODS: This cross-sectional study was performed on 96 infertile men referring to infertility treatment center of Kashan University of Medical Sciences during March 2017 till September 2017 in Iran. Semen analysis and diagnostic PCR test were performed for detection of HPV DNA. The semen parameters in HPV infected and ASA positive samples were compared with HPV non-infected and ASA negative samples. Chi square test was used to determine the correlation between variables and p<0.05 was considered statistically significant. RESULTS: HPV DNA and ASA were detected in 17.4% and 15.2% of 96 semen samples, respectively. Semen volume, sperm count, sperm motility and the normal morphology rate were significantly decreased in HPV-positive subjects (p=0.004, p= 0.016, p<0.001, and p=0.017, respectively). Also, sperm motility was significantly decreased in ASA-positive subjects (p=0.002), also patients with HPV infection had a higher rate of ASA than the non-HPV group. In contrast to ASA, HPV infection had a significant correlation with education level (p=0.039). CONCLUSION: The findings suggest that asymptomatic seminal infection of HPV and ASA by adversely affecting sperm quality, in particular sperm motility and count, may play an important role in male infertility.

A Real-Time RT-PCR Assay for Genotyping of Rotavirus

Background: Human rotavirus (HRV) is the causative agent of severe gastroenteritis in children and responsible for two million hospitalizations and more than a half-million deaths annually. Sequence characteristics of the gene segments encoding the VP7 and VP4 proteins are used for the genotype classification of rotavirus. A wide variety of molecular methods are available, mainly based on reverse transcription PCR for rapid, specific and sensitive genotyping of rotaviruses. This study describes an alternative real-time PCR assay for genotyping of rotavirus. Methods: The samples of stools studied in this research have been collected from patients referred to Children's Medical Centers, Tehran, Iran. Rotavirus detection and genotyping were performed using the RT-PCR and semi-nested RT-PCR, respectively. Samples were then genotyped with a new real-time PCR. Results: The real-time PCR was able to genotype all positive samples with a mean Ct of 28.2. Besides, a concordance rate of 100% was detected between real-time PCR and semi-nested RT-PCR. Conclusion: In this study, the genotyping of rotavirus with real-time PCR showed that this method can provide several favorable features, including high sensitivity and specificity, and a wide dynamic range for rotavirus genotyping.

Laboratory Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study.

INTRODUCTION: The role of laboratory parameters in screening of COVID-19 cases has not been definitely established. This study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive RT-PCR for COVID-19. METHODS: This diagnostic accuracy study was conducted on suspected COVID-19 patients, who presented to Behpooyan Clinic Medical center in Tehran (Iran) from 22 February to 14 March, 2020. Patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19, and the accuracy of different laboratory parameters in predicting cases with positive RT-PCR was evaluated using area under the ROC curve (AUC). RESULTS: Two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). The result of RT-PCR for COVID-19 was positive in 70 (35%) cases. Patients with positive RT-PCR had significantly higher neutrophil (NEU) count (p = 0.0001), and C-reactive protein (CRP) (p = 0.04), lactate dehydrogenase (LDH) (p = 0.0001), aspartate aminotransferase (AST) (p = 0.001), alanine aminotransferase (ALT) (p = 0.0001), and Urea (p = 0.001) levels in serum. In addition, patients with positive RT-PCR had lower white blood cell (WBC) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. ALT (AUC = 0.879), CRP (AUC = 0.870), NEU (AUC = 0.858), LDH (AUC = 0.835), and Urea (AUC = 0.835) had very good accuracy in predicting cases with positive RT-PCR for COVID-19, respectively. CONCLUSION: Our findings suggest that level of LDH, CRP, ALT and NEU can be used to predict the result of COVID-19 test. They can help in detection of COVID-19 patients.

High Frequency of Aichivirus in Children With Acute Gastroenteritis in Iran.

BACKGROUND: Initially, detection and isolation of Aichivirus as a new member of Picornaviridae family was documented in Japan. Aichivirus species belongs to genus Kobuvirus, including 3 genotypes A, B and C. In previous studies, it has been suggested that Aichivirus infect humans by fecal-oral route. To establish an investigation for the occurrence of Aichivirus among pediatric patients involved to acute gastroenteritis, we developed a reverse transcription quantitative polymerase chain reaction assay for detection and quantification of Aichivirus in stool specimens. MATERIAL AND METHODS: In this study, a total of 160 stool samples from September 2018 to May 2019 were collected from pediatric patients presenting with acute gastroenteritis in Karaj hospital, Iran. After viral RNA extraction, the reverse transcription quantitative polymerase chain reaction was performed to amplify the 3CD junction region of Aichivirus genome and viral load was assessed. Aichivirus genomic RNA was detected in 13/160 (8.1%) of stool samples. The highest Aichivirus detection rate was in December (30.7%). The maximum viral load was determined to be 3.9 × 10 copies/g in one sample obtained from a 1-month-old patient. The co-infection of Aichivirus with salivirus and saffold virus was also assessed by reverse transcription quantitative polymerase chain reaction, among which frequent mixed infections by 2 or more viruses were identified. CONCLUSIONS: This is the first documentation of Aichivirus detection in stool samples that demonstrates Aichivirus has been circulating among Iranian pediatric patients.

Prevalence of astrovirus, adenovirus, and sapovirus infections among Iranian children with acute gastroenteritis.

AIM: This study aimed to determine the prevalence of Human Astroviruses (HAstVs), enteric Adenoviruses (HAdVs), and Sapoviruses (SaVs) in acute diarrhea patients, as well as their relation to age, sex, and season. BACKGROUND: Acute gastroenteritis is one of the most common diseases affecting children <5 years old and viral agents with approximately >75% are the major causative agent of acute infectious diarrhea. After Rotavirus and Norovirus, the greater viral agents of acute gastroenteritis include HAstVs, HAdVs, and SaVs. To the best of our knowledge, there are sparse studies in Iran detecting at least three enteric viruses as causative agents of diarrhea simultaneously. METHODS: The sample was collected from children referring to pediatric medical centers in Tehran, Iran; they were tested for Astrovirus, enteric Adenovirus, and Sapovirus by conventional PCR method. The association of incidence of viral enteric agents was evaluated with age, sex and seasonal pattern in children <5 years old. RESULTS: The positive case number among acute gastroenteritis patients was 17/120 (14.1%). Patients ranged in age within 1-60 months, but 52.9% were aged ≤ 12 months. Males comprised the majority (70.6), and the male: female ratio was 2.4. HAstV was the most frequently detected virus (6.7%), while SaVs were detected only in 2.5% of cases. Mixed infections were not detected in these samples. The highest rate of HAstV was identified in winter (66.7%), HAdV in fall (66.7%), and SaV in winter (33.3%). CONCLUSION: These findings underscore the importance of monitoring the epidemiology of HAstV, HAdV, and SaV as causative agents of viral diarrhea infections.

Detection and characterization of rotavirus G and P types from children with acute gastroenteritis in Qom, central Iran.

AIM: The aim of the study is to estimate the burden of Rotavirus gastroenteritis as well as predominant genotypes of Rotavirus among children less than 5 years of age referring to Pediatric University Hospital in Qom, Iran. BACKGROUND: Gastroenteritis is the fourth most common cause of death and accounts for 16% of all deaths in children <5 years of age worldwide. METHODS: During two years, 130 patients referring to a pediatric hospital were enrolled in this study. After RNA extraction, Rotaviruses were detected by the VP6 gene. Then, G-typing (G1, G2, G3, G4, G8, G9, and G12) and P-typing (P4, P6, and P8) were performed using RT-PCR and specific primers. RESULTS: The results of the PCR revealed that from a total of 130 patients, 22 cases (16.9%) showed positive VP6 by RT-PCR. G1 was mostly the predominant serotype (27%), accounting for 22% of all VP7-positive isolates, followed by G9 (18%), G2 (9%), G3 (9%), and G4 (9%). None of the strains revealed the presence of G8 genotype (0%), and 5 specimens (23%) were non-typable. The frequency of P typing was P8 (50%), P6 (23%), P4 (14%), and 3 samples were P-non-typable (13%), respectively. The dominant G-P combination was G1 [8] (32%). CONCLUSION: Such studies based on typing methods assists in the Rotavirus vaccine introduction by policymakers and design of new effective vaccines.

Optimization of RT-qPCR for Detection of Aichi Virus in Sewage and River Water Samples in Karaj, Iran.

BACKGROUND: Aichi virus (AiV) is an emerging virus, which belongs to Kobuvirus genus of the Picornaviridae family. AiV was recently determined as an etiologic agent of gastroenteritis in susceptible humans. After shedding of virus particles from affected people, AiV particles can contaminate water sources. Then, infection with this virus occurs in humans by the fecal-oral route after exposure with contaminated waters. Thus far, some research around the world demonstrated that different kinds of water sources including river water, ground water and treated or untreated sewage water have contamination with AiVs. Molecular detection of AiV has been mostly depended on reverse transcription polymerase chain reaction (RT-PCR) methods, which targeted 3CD junction region of the virus genome. METHODS: The present study aims to assess the molecular detection of AiVs in treated and untreated sewage water and river water specimens by the development of reverse transcription-quantitative PCR (RT-qPCR) assay for all AiV genotypes. RESULTS: Out of 50 samples tested (consisting of 28 river water samples and 22 sewage water samples), the AiV genomic RNA was identified in 15/28 (~50%) river water samples and in 14/22 (~70%) sewage samples. CONCLUSION: Our results, for the first time, indicate that AiVs have been circulating in Iran.

Optimization of non-detergent treatment for enveloped virus inactivation using the Taguchi design of experimental methodology (DOE).

In mammalian cell culture technology, viral contamination is one of the main challenges; and, so far, various strategies have been taken to remove or inactivate viruses in the cell-line production process. The suitability and feasibility of each method are determined by different factors including effectiveness in target virus inactivation, maintaining recombinant protein stability, easiness-in terms of the process condition, cost-effectiveness, and eco-friendliness. In this research, Taguchi design-of-experiments (DOE) methodology was used to optimize a non-detergent viral inactivation method via considering four factors of temperature, time, pH, and alcohol concentration in an unbiased (orthogonal) fashion with low influence of nuisance factors. Herpes Simplex Virus-1 (HSV1) and Vero cell-line were used as models for enveloped viruses and cell-line, respectively. Examining the cytopathic effects (CPE) in different dilutions showed that pH (4), alcohol (15%), time (120 min), and temperature (25 °C) were the optimal points for viral inactivation. Evaluating the significance of each parameter in the HSV-1 inactivation using Taguchi and ANOVA analyses, the contributions of pH, alcohol, temperature and time were 56.5%, 19.2%, 12%, and 12%, respectively. Examining the impact of the optimal viral treatment condition on the stability of model recombinant protein-recombinant human erythropoietin, no destabilization was detected.

Occurrence of Salivirus in Sewage and River Water Samples in Karaj, Iran.

Salivirus is a newly discovered virus which seems to be related to acute gastroenteritis in children. Salivirus may infect susceptible children by fecal-oral route after exposure to contaminated water. The present study aims to evaluate the occurrence and quantity of Salivirus in treated and untreated sewage water and river water samples collected in the city of Karaj, Iran by reverse transcription-quantitative PCR assay. A total of 50 samples were collected from environmental waters containing 22 treated and untreated sewage water in volume of 1 l and 28 river water samples in volume of 5 l were included in this study. After viral RNA extraction, the Real-time PCR was performed to amplify the 5'UTR sequence of Salivirus genome and viral load was assessed. Out of the 50 samples tested, the Salivirus genomic RNA was identified in 5/12 (41.6%) of treated and 3/10 (30%) of untreated sewage samples and in 8/28 (28.5%) of river water samples. The maximum viral load was 4.8 × 106 copies/l in treated sewage water sample in September and the lower viral load was 4 × 105 copies/l related to treated sewage water taken in December. This is the first report of Salivirus occurrence in the environmental waters in Iran. The viral prevalence of Salivirus in each of the three sets of tested samples was within low to moderate in range.

Association of IL28B (IFNL3) rs12979860 mRNA levels, viral load, and liver function among HCV genotype 1a patients.

AIM: The present study was designed to evaluate the correlation of interleukin 28B (IL28B, IFNL3) rs12979860 mRNA levels, viral load, and liver function among hepatitis C virus (HCV) patients genotype 1a. BACKGROUND: HCV is considered essentially hepatotropic and is a major health problem around the world. METHODS: This study included 100 HCV-infected patients with HCV genotype1a (G1a) and rs12979860 CC genotype. These patients were divided into two groups according to HCV treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and HCV Load were measured and recorded for each patient. IL28B mRNA levels were determined using real-time polymerase chain reaction assay, and their correlation with clinical data were analyzed. STRING was applied to construct a network and identify interactions between IL28B (IFNL3) and its significant neighbor proteins. RESULTS: The results revealed a significant relationship between the ALT as well as ALP levels with IL28B rs12979860 mRNA expression level in men, and also with age >50 years. In the treated group, AST level and HCV load had a significant relationship with IL28B mRNA expression level. The results showed that the level of ALP and AST decreased significantly with increased IL28B mRNA expression level in the treated and untreated group, respectively. STRING database showed that IL28B (IFNL3) interacted with ten important neighbor proteins with some of these proteins being involved in signal transduction pathway activating antiviral response. CONCLUSION: This study indicated that rs12979860CC genotype could predict IL28B mRNA expression level in HCV-infected patients with G1a. Furthermore, IL28B mRNA expression level may serve as a useful marker for the development of G1a HCV-associated outcomes.

Impact of HIV infection in patients infected with chronic HCV (genotypes 1a and 3a): virological and clinical changes.

BACKGROUND: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection has become a serious public health problem. The influence of HIV/HCV coinfection on plasma HCV RNA loads and clinical criteria which are usually regarded as a predictor of the progress of liver disease have not been reliably evaluated. OBJECTIVES: This study investigated the impact of HIV infection on HCV RNA load and clinical indexes in Yazd and Tehran. MATERIALS AND METHODS: HCV/HIV-coinfected patients and HCV-monoinfected controls were examined and compared for plasma HCV RNA and related risk factors such as HCV genotypes, liver enzymes, and transmission routes. RESULTS: A total of 54 HCV/HIV-coinfected patients and 88 HCV-monoinfected controls were studied. The HCV RNA load mean was significantly higher in HCV/HIV-coinfected patients than in HCV-monoinfected patients (p < 0.001). HCV RNA load mean in patients infected with HCV without anti-HCV therapy was lower than HIV/HCV patients with and without highly active antiretroviral therapy that this difference was significant (p < 0.001). The HCV RNA levels were significantly higher in HIV/HCV genotype 3a coinfected patients than in genotype 3a monoinfected patients (p < 0.001). HIV RNA levels were lower in genotype 1a infected patients than in genotype 3a infected patients, but this difference was not significant statistically. The ALT mean levels were significantly higher in genotype 3a HIV/HCV-coinfected patients than in genotype 3a HCV-monoinfected patients (p < 0.001). CONCLUSIONS: HIV/HCV coinfection leads to a significant increase in plasma HCV RNA. Further evaluations of the effects of ART and HIV infection on the course of HCV infection and the response to treatment against HCV infection in other and different genotypes are also needed. Moreover, HIV-infected patients should be screened regularly for HCV coinfection, particularly if they are in high-risk groups such as IDUs and recipients of blood transfusions.

Epidemiology of Rotavirus-Norovirus Co-Infection and Determination of Norovirus Genogrouping among Children with Acute Gastroenteritis in Tehran, Iran.

BACKGROUND: Enteric viruses, particularly human rotavirus and norovirus, have been shown to replace bacteria and parasites, as the most common pathogens responsible for acute diarrhea. However, there are still few epidemiological data on the simultaneous occurrence of these viruses in Iran. In this regard, the aim of this study was to assess the useful epidemiological data on the gastroenteritis associated with rotavirus-norovirus mixed infection and to examine the prevalence of norovirus genogrouping among children aged less than five years old in Iran. METHODS: A total of 170 stool samples were collected from children under five years of age with the clinical signs and symptoms of acute gastroenteritis, from May 2013 to May 2014. For the detection of both rotavirus and norovirus, total RNA was extracted from all samples, followed by reverse transcription polymerase chain reaction (RT-PCR). For both detected rotaviruses and noroviruses, genogrouping was performed. RESULTS: Of 170 samples, 49 (28.8%) and 15 (8.8%) samples were found to be positive for rotavirus and norovirus infections by RT-PCR. Interestingly, 6 (3.5%) patients were positive for both infections. Among the 15 norovirus-positive patients, 13 (86.6%) and 2 (13.3%) belonged to genogroups GII and GI. CONCLUSIONS: The norovirus genogroup GII and rotavirus lead to the serious infections in children with acute gastroenteritis. However, more well-designed studies are needed to further elucidate the role of other enteric viruses in acute gastroenteritis.