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Poliovirus infection causes dramatic changes in host cells, including inhibition of host protein secretion. To identify poliovirus variants (Sin−) that do not block host secretion, Burgon et al. (p. 10129-10139) performed a fluorescence-activated cell sorter-based selection for Sin− phenotype variants with robust growth properties. In addition to the desired Sin− mutation, they also found a mutation that confers rapid spread by increasing the rate of cell death. This mutation maps to proteinase 2A, increases viral spread in several genetic backgrounds, and suggests a new function for the 2A protein in inhibiting virus-induced apoptosis.
Sequences in the herpes simplex virus 1 (HSV-1) latency-associated transcript (LAT) region are responsible for key phenotypic differences in HSV-1 and HSV-2 latency, including site-specific reactivation and latent gene expression in different sensory neuronal subtypes. Using HSV-1/HSV-2 chimeric viruses, Bertke et al. (p. 10007-10015) show that sequences required for the expression of both phenotypes reside directly downstream of the LAT TATA element and overlap the 5′ end of LAT exon 1. Further study of this short genomic region is likely to yield insight into mechanisms by which the HSV LAT exerts its effects on viral latency and reactivation.
The adenovirus E1B-55K and E4orf6 proteins promote viral late protein synthesis, yet a direct relationship with cellular translational machinery has not been described. Spurgeon and Ornelles (p. 9970-9982) report that the E1B-55K and E4orf6 proteins limit eIF2α phosphorylation mediated by the RNA-dependent protein kinase PKR at late times of infection. This function correlates with the efficiency of viral late protein synthesis and requires a cullin 5-mediated activity of the E1B-55K/E4orf6 viral ubiquitin ligase complex. These findings expand an understanding of how the E1B-55K and E4orf6 proteins promote viral gene expression and underscore the importance of these proteins in regulating the cellular response during the late phase of infection.
Viruses and bacteria often share ecological niches, but their mutual impact on growth and pathogenicity is poorly understood. Lidsky et al. (p. 9940-9951) demonstrate that encephalomyocarditis virus (but not poliovirus) elicited, in mycoplasma-contaminated cells, intense DNA degradation reminiscent of that observed upon apoptosis. Remarkably, this process is caused by a DNase of mycoplasma origin. In the absence of viral infection, the mycoplasma DNase is dormant. This virus-mycoplasma “cooperation” illustrates the complexity of pathogen-host interactions when viruses and bacteria infect the same host.
The extensive sequence divergence of influenza A viruses has hindered the simultaneous reverse transcription (RT)-PCR amplification of the eight genomic RNA segments that compose its genome. Zhou et al. (p. 10309-10313) developed a multisegment RT-PCR method that simultaneously amplifies the eight genomic RNA segments of influenza virus, irrespective of the virus subtype and lineage. Plasmids used to genetically engineer influenza viruses were modified to incorporate these amplicons. These technologies were combined to rapidly generate recombinant human H3N2 and swine origin H1N1 viruses directly from swab specimens. This approach will speed influenza A virus sequence analysis and production of new vaccines.