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J Virol. 2016 October 15; 90(20): 8949.
Published online 2016 September 29. doi:  10.1128/JVI.01647-16
PMCID: PMC5044819

Articles of Significant Interest Selected from This Issue by the Editors

Delving Deeper into Viral Population Dynamics

RNA virus populations can be composed of hundreds of millions of infectious viral particles. This large population size, combined with the high error rate of RNA virus replication, results in the vast majority of possible mutations in a viral population existing at very low frequency. Conventional next-generation sequencing (NGS) lacks the sensitivity to separate true low-frequency variants from noise. Whitfield and Andino (p. 8950–8953) describe circular sequencing (CirSeq), a method to reduce the error rate associated with NGS, thus allowing for the accurate detection and characterization of low-frequency variants in a viral population.

figure zjv0201620650001
Error detection and correction of genetic data by adding some redundancy (i.e., extra sequencing data).

Insights into Phage [var phi]29 and Bacillus subtilis Interactions from Transcriptional Profiling

A comprehensive understanding of virus-host relationships requires the study of associated transcriptional changes. Mojardín and Salas (p. 9293–9304) performed a high-resolution analysis of [var phi]29 and Bacillus subtilis transcriptomes. Bacterial repressed genes are involved in the utilization of specific carbon sources, suggesting that optimal phage [var phi]29 replication depends on the carbon source that its host uses during infection. Previously uncharacterized viral antisense transcripts add a new layer to the [var phi]29 transcriptome complexity.

figure zjv0201620650002
Interaction networks of B. subtilis proteins encoded by differentially expressed genes after [var phi]29 infection.

Japanese Macaque Rhadinovirus Encodes a MicroRNA miR-17 Mimic

Japanese macaque rhadinovirus (JMRV) is a gammaherpesvirus linked to Japanese macaque encephalomyelitis, a disease akin to multiple sclerosis. Skalsky et al. (p. 9350–9363) report the identification of 15 microRNAs (miRNAs) produced by JMRV during lytic replication and demonstrate that one of the viral miRNAs mimics the activity of the cellular miR-17 family. These findings provide insight into some of the regulatory functions of rhadinovirus 2 miRNAs and provide an important step toward understanding viral miRNA functions in primates.

figure zjv0201620650003
Alignment of JMRV miR-J8-3p with cellular miR-17 family members.

Host E3 Ubiquitin Ligase ITCH Regulates Egress of Ebola Virus Particles

The VP40 matrix protein of Ebola virus (EBOV) orchestrates virion assembly and budding in part by recruiting host proteins that facilitate virus egress and spread. Han et al. (p. 9163–9171) identify the host E3 ubiquitin ligase ITCH as a specific EBOV VP40 interactor, highlighting the physical and functional interplay of cellular E3 ligases, ubiquitylation, and regulation of VP40-mediated egress. This virus-host relationship enhances an understanding of the biology and pathogenesis of this emerging pathogen and may represent a new target for host-oriented, small-molecule inhibitors of filovirus egress.

figure zjv0201620650004
Budding of recombinant VSV-EBOV is reduced significantly in ITCH knockout cells.

HIV Persists in Tissues during Drug Therapy

HIV genome diversity during antiviral drug suppression is not well understood. Rose et al. (p. 8984–8993) detected HIV DNA in 65% of 229 postmortem tissues sampled from 20 antiviral-treated individuals with no detectable viral load at death. Tissue-based HIV (DNA and RNA) continued to evolve at the same rate as that reported for untreated individuals. No genetic evidence for drug resistance was identified, suggesting that tissues are shielded from antiviral drugs. HIV RNA was visualized in cerebellum and lymph node tissue. These results reinforce the importance of tissues as a target for anti-HIV therapies.

figure zjv0201620650005
RNAscope of cells expressing HIV gag-pol transcripts (pink) in cerebellum tissue.

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)