Journal of Virology, June 2008, p. 5671, Vol. 82, No. 12
0022-538X/08/$08.00+0 doi:10.1128/JVI.00850-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Uncapped Poliovirus mRNA Is Remarkably Stable in 2APro-Modified PolysomesPositive-strand RNA viruses must protect their viral mRNA from host mRNA turnover pathways to enable subsequent RNA replication. In companion studies, Kempf and Barton (p. 5835-5846 and p. 5847-5859) found that poly(rC) binding protein bound to the 5' end of naturally uncapped poliovirus mRNA blocks 5' exonucleases as ribosomes initially traverse the open reading frame during de novo viral polysome formation. Additionally, viral mRNA stability is enhanced coincident in time with cleavage of eIF4G I and II in 2AProtease-modified polysomes. This work provides insights into mechanisms by which positive-strand viruses uncouple viral mRNA translation from host mRNA turnover pathways.
Cell Cycle and Translational Requirements for Vesicular Stomatitis Virus Oncolysis in T Cells
Vesicular stomatitis virus (VSV) is a candidate oncolytic virus that selectively replicates and induces cell death in cancer cells. VSV infection induces apoptosis in T lymphocytes from patients with adult T-cell leukemia but not in resting T cells. Using primary T lymphocytes and pharmacological inhibitors, Oliere et al. (p. 5735-5749) demonstrate that VSV replication in primary lymphocytes is dependent on cell cycle transition from the G0 to G1 phase and global enhancement of protein synthesis via mTOR and eIF4E activity. These results provide the rationale to explore additional combinatorial approaches to overcome the resistance of different cancers to oncolytic virus therapy.
Major Homology Region Participates in Formation of the Mature Retrovirus Capsid
During retroviral maturation, the capsid protein CA undergoes dramatic structural changes and rearranges to form unique intermolecular interfaces in the mature capsid shell. Using an in vitro assembly approach, Purdy et al. (p. 5951-5961) demonstrate that purified Rous sarcoma virus CA protein assembles into structures resembling authentic mature capsids. Hydrophobic residues within the major homology region (MHR) serve a critical function in controlling this process. The properties of second-site substitutions that suppress lethal MHR phenotypes provide important new insights into the molecular events of capsid formation.
A Conformational Switch in øX174 Scaffolding Protein Is Required for Virion Morphogenesis
In the øX174 procapsid, the external scaffolding protein forms a non-quasiequivalent lattice around a T=1 structure. To achieve this unique arrangement, specific scaffolding subunits must undergo a distinct conformational switch. Cherwa et al. (p. 5774-5780) generated mutant proteins designed to inhibit the switch and expressed them in cells infected with wild-type virus. The mutant proteins acted as potent inhibitors of viral replication directing assembly intermediates off the morphogenetic pathway. Extragenic resistance mutants were also characterized. This study validates an approach in which viral proteins are modified into assembly inhibitors and elucidates one possible mode of resistance that can be anticipated.
Primate Foamy Viruses Replicate in Terminally Differentiated Oral Epithelial Cells
Foamy viruses (FV) are retroviruses that establish nonpathogenic infections in their hosts but highly cytopathic infections in vitro. Murray et al. (p. 5981-5985) used in situ hybridization to identify the cell type in which FV replicates in naturally infected rhesus macaques. They show that the only cells in which viral RNA can be detected are superficial epithelial cells of the oral mucosa, a cell type that is rapidly shed into saliva. This site of replication allows for viral dissemination without compromising the health of the host.
Journal of Virology, June 2008, p. 5671, Vol. 82, No. 12
0022-538X/08/$08.00+0 doi:10.1128/JVI.00850-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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