Recombinant origin and interspecies transmission of a HERV-K(HML-2)-related primate retrovirus with a novel RNA transport element.

HERV-K(HML-2), the youngest clade of human endogenous retroviruses (HERVs), includes many intact or nearly intact proviruses, but no replication competent HML-2 proviruses have been identified in humans. HML-2-related proviruses are present in other primates, including rhesus macaques, but the extent and timing of HML-2 activity in macaques remains unclear. We have identified 145 HML-2-like proviruses in rhesus macaques, including a clade of young, rhesus-specific insertions. Age estimates, intact ORFs, and insertional polymorphism of these insertions are consistent with recent or ongoing infectious activity in macaques. 106 of the proviruses form a clade characterized by an ~750 bp sequence between env and the 3' LTR, derived from an ancient recombination with a HERV-K(HML-8)-related virus. This clade is found in Old World monkeys (OWM), but not great apes, suggesting it originated after the ape/OWM split. We identified similar proviruses in white-cheeked gibbons; the gibbon insertions cluster within the OWM recombinant clade, suggesting interspecies transmission from OWM to gibbons. The LTRs of the youngest proviruses have deletions in U3, which disrupt the Rec Response Element (RcRE), required for nuclear export of unspliced viral RNA. We show that the HML-8 derived region functions as a Rec-independent constitutive transport element (CTE), indicating the ancestral Rec-RcRE export system was replaced by a CTE mechanism.

Transcriptomic analysis reveals regulation of adipogenesis via long non-coding RNA, alternative splicing, and alternative polyadenylation.

Obesity is characterized by dysregulated adipogenesis that leads to increased number and/or size of adipocytes. Understanding the molecular mechanisms governing adipogenesis is therefore key to designing therapeutic interventions against obesity. In our study, we analyzed 3'-end sequencing data that we generated from human preadipocytes and adipocytes, as well as previously published RNA-seq datasets, to elucidate mechanisms of regulation via long non-coding RNA (lncRNA), alternative splicing (AS) and alternative polyadenylation (APA). We discovered lncRNAs that have not been previously characterized but may be key regulators of white adipogenesis. We also detected 100 AS events and, using motif enrichment analysis, identified RNA binding proteins (RBPs) that could mediate exon skipping-the most prevalent AS event. In addition, we show that usage of alternative poly(A) sites in introns or 3'-UTRs of key adipogenesis genes leads to isoform diversity, which can have significant biological consequences on differentiation efficiency. We also identified RBPs that may modulate APA and defined how 3'-UTR APA can regulate gene expression through gain or loss of specific microRNA binding sites. Taken together, our bioinformatics-based analysis reveals potential therapeutic avenues for obesity through manipulation of lncRNA levels and the profile of mRNA isoforms via alternative splicing and polyadenylation.

Alarming Situation of Spreading Enteric Viruses Through Sewage Water in Dhaka City: Molecular Epidemiological Evidences.

Global burden of acute viral gastroenteritis remains high, particularly in developing countries including Bangladesh. Sewage water (SW) is an important node to monitor enteric pathogens both in the environment and among the population. Analysis of SW in Dhaka city deems crucially important because a large number of urban-city dwellers live in Dhaka city, the capital of Bangladesh, under a constant threat of precarious sewerage system. In this study, we collected raw SW from five locations of Dhaka city every month from June 2016 to May 2017. It was concentrated with polyethylene glycol (PEG) and investigated for three major enteric viruses, rotavirus A (RVA), norovirus GII (NoV GII) and adenovirus (AdV) using polymerase chain reaction (PCR). Most of these SW samples collected from both hospitals and non-hospital areas yielded enteric viruses: 76% samples were positive for AdV, followed by 53% NoV GII and 38% RVA. Viral load was determined as much as 1 × 107 copies/ml for RVA and 3.5 × 103 copies/ml for NoV GII. Importantly, NoV GII and AdV that can affect people of all ages were predominated during monsoon also when SW overflows and spreads over a wide and crowded area. Genotypes G1, G2, G3, G8, and G9 for RVA, GII.4 for NoV, and type 41 for AdV were detected representing the current profile of circulating genotypes in the population. This study provides the first evidence of distribution of major diarrheal viruses in SW in Dhaka city which is alarming showing grave risk of impending outbreaks through exposure.