Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation

The HCV internal ribosome entry site (IRES) spans a region of ∼340 nt that encompasses most of the 5′ untranslated region (5′UTR) of the viral mRNA and the first 24–40 nt of the core-coding region. To investigate the implication of altering the primary sequence of the 5′UTR on IRES activity, naturally occurring variants of the 5′UTR were isolated from clinical samples and analyzed. The impact of the identified mutations on translation was evaluated in the context of RLuc/FLuc bicistronic RNAs. Results show that depending on their location within the RNA structure, these naturally occurring mutations cause a range of effects on IRES activity. However, mutations within subdomain IIId hinder HCV IRES-mediated translation. In an attempt to explain these data, the dynamic behavior of the subdomain IIId was analyzed by means of molecular dynamics (MD) simulations. Despite the loss of function, MD simulations predicted that mutant G266A/G268U possesses a structure similar to the wt-RNA. This prediction was validated by analyzing the secondary structure of the isolated IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg2+ ions. These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation

Translation efficiencies of the 5 '-untranslated region of genotypes 1a and 3a in hepatitis C infected patients

Differences between the translation efficiencies mediated by the 5'-untranslated regions (5'UTR) of genotypes (gt) 1 and 3 of hepatitis C virus (HCV) have been reported but it is unknown if such differences are biologically significant. The 5'-UTR was sequenced from paired serum and liver samples from 26 patients with chronic HCV hepatitis (11 gt la, 15 gt 3a). To determine whether there is a consistent difference between gts 1a and 3a translation efficiency, 5'-UTR (nt 1-356) and 5'-UTR plus core (nt 1-914) sequences were cloned into bicistronic, luciferase-encoding constructs and relative translation efficiencies (RTE) measured in Huh7 cells and BHK cells. The relationships between viral load, liver biopsy Ishak scores, degree of steatosis and translational activity of the patient-derive nucleotide sequence were examined. There were no differences in 5'-UTR sequence between serum and corresponding liver samples. The mean RTE of 5'-UTR sequences from gt 3a isolates was not significantly different from gt la whether or not the core encoding sequence was included, although inclusion of core led to a reduction in RTE by 93-97% for both genotypes. No correlation was found between RTE and serum HCV RNA levels, liver steatosis, inflammation, or fibrosis. However, a significant correlation was found between the presence of steatosis and infection with HCV gt 3a. It is concluded that there was no difference in translation efficiencies of 5'-UTRs from patients infected with gts 1 a and 3a, and translation activity measured in vitro does not correlate with viral load or severity of liver disease

BK polyomavirus genotypes in renal transplant recipients in the United States: A meta‐analysis

Background: In the United States, increasing ethnic diversity has been apparent. However, the epidemiology and trends of BKV genotypes remain unclear. This meta-analysis was conducted with the aim to assess the prevalence of BKV genotypes among kidney transplant (KTx) recipients in the United States. Methods: A comprehensive literature review was conducted through October 2018 utilizing MEDLINE, Embase, and Cochrane Database to identify studies that reported the prevalence of BKV subtypes and/or subgroups in KTx recipients in the United States. Pooled prevalence rates were combined using random effects, generic inverse variance method. The protocol for this study is registered with PROSPERO (no. CRD42019134582). Results: A total of eight observational studies with a total of 193 samples (urine, blood, and kidney tissues) from 188 BKV-infected KTX recipients were enrolled. Overall, the pooled estimated prevalence rates of BKV subtypes were 72.2% (95% confidence of interval [CI]: 62.7-80.0%) for subtype I, 6.8% (95% CI: 2.5-16.9%) for subtype II, 8.3% (95% CI: 4.4-15.1%) for subtype III, and 16.1% (95% CI: 10.4-24.2%) for subtype IV, respectively. While metaregression analysis demonstrated a significant positive correlation between year of study and the prevalence of BKV subtype I (slopes = +0.1023, P =.01), there were no significant correlations between year of study and percentages of BKV subtype II-IV (P \u3e.05). Among KTx recipients with BKV subtype I, the pooled estimated percentages of BKV subgroups were 22.4% (95% CI: 13.7-34.5%) for subgroup Ia, 30.6% (95% CI: 17.7-47.5%) for subgroup Ib1, 47.7% (95% CI: 35.8-59.9%) for subgroup Ib2, and 4.1% (95% CI:1.2-13.3%) for subgroup Ic, respectively. Conclusion: BKV subtype I is the most prevalent subtype among KTx recipients in the United States and its prevalence seems to increasing overtime. Subgroup Ib2 is the most common subgroup among BKV subtype I

Epidemiology of hepatitis B in pregnant Iranian women: a systematic review and meta-analysis

Perinatal transmission is one of the most common routes of hepatitis B virus (HBV) transmission. This study aims to identify the epidemiological features of HBV among pregnant Iranian women. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two authors independently searched several online databases without time limit until May 2017. The databases include Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed, Science Direct, Cochrane, Web of Science and Google Scholar. The data were analyzed based on a random-effects model using Comprehensive Meta-Analysis software version 2. Thirty-seven studies were included in the meta-analysis. The prevalence of HBV among pregnant Iranian women was 1.18 (95 CI: 0.09-1.53). The prevalence of HBV among pregnant women living in urban and rural areas was 1.60 (95 CI: 0.06-4.30) and 1.70 (95 CI: 0.09-3.2), respectively. The prevalence of HBV among housewives and working pregnant women was 4.3 (95 CI: 1.4-12.5) and 1.2 (95 CI: 0.02-5.8), respectively. The risk of developing an HBV infection was significantly associated with illiteracy (p = 0.013), abortion (p = 0.001), blood transfusion (p < 0.001) and addicted spouse (p = 0.045). However, no significant relationship was observed between HBV infection and urbanization (p = 0.65), occupation (p = 0.37), history of surgery (p = 0.32) or tattooing (p = 0.69). Vaccination coverage (receiving at least a single dose) in pregnant women was 9.8 (95 CI: 5.3-17.5). The prevalence of HBV among pregnant women is lower than in the general population of Iran. HBV vaccination coverage was low among pregnant Iranian women. Therefore, health policy-makers are recommended to enforce immunization programs for HBV vaccination among high-risk pregnant women