Journal of Virology, August 2008, p. 7757, Vol. 82, No. 16
0022-538X/08/$08.00+0 doi:10.1128/JVI.01265-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Vaccinia Virus Entry via Fluid-Phase Endocytosis and Virus Penetration FactorVaccinia virus infects many cell lines in culture and animal species in vivo, but its cell entry pathway remains unclear. Huang et al. (p. 7988-7999) show that vaccinia intracellular mature virions bind to the filopodia of HeLa cells, move toward the cell body, and enter by fluid-phase endocytosis. A cellular protein, vaccinia virus penetration factor, was found to play an important role in this cell entry process. This work provides new insights into the endocytic pathway exploited by vaccinia virus for cell entry.
Coronavirus nsp16 Is Involved in Viral RNA Capping
The coronavirus family encodes viral nonstructural proteins that participate in the capping of viral RNA. Decroly et al. (p. 8071-8084) demonstrate that nsp16 mediates cap-0 to cap-1 S-adenosyl-L-methionine-dependent RNA 2'-O-methyltransferase activity. The catalytic tetrad and other key residues essential for cap-0-specific binding were identified by bioinformatics and mutagenesis studies. The results suggest that coronavirus RNA capping follows a natural order in which the 2'-O-methyltransfer must be preceded by guanine-N7 methylation by an as-yet-unknown enzyme.
Human Papillomavirus Type 16 E1^E4 Amyloid Structure Explains Protein Abundance
The human papillomavirus (HPV) E1^E4 protein accumulates during productive infection and is thought to aid virus egress from the epithelial surface by binding and reorganizing the cellular cytokeratin network. McIntosh et al. (p. 8196-8203) provide the first structural analysis of HPV type 16 E1^E4 protein and show that the loss of N-terminal amino acids, which occurs during epithelial differentiation, stimulates its assembly into insoluble amyloid-like fibers by relieving structural constraints. This work provides a molecular basis for E1^E4 accumulation and cytokeratin reorganization and suggests a role for amyloid imaging probes in the diagnosis of HPV infection.
Role of Japanese Encephalitis Virus prM N Glycosylation in Virus Replication and Pathogenesis
The Japanese encephalitis virus (JEV) prM protein, a precursor of the membrane-anchored and virion-associated M protein, contains a single N-glycosylation motif within the pr region that is highly conserved among flaviviruses. Kim et al. (p. 7846-7862) show that this N-glycosylation motif and its N-glycan substituents serve a spectrum of critical functions in JEV infection, including facilitating viral particle release and prM protein biogenesis in a cell-type-specific fashion as well as influencing viral pathogenesis in mice. These findings demonstrate the functional importance of the prM N-glycosylation consensus sequence in the replication and pathogenesis of JEV and possibly other closely related flaviviruses.
Vicriviroc Resistance in an Human Immunodeficiency Virus Type 1 Subtype C-Infected Subject
Vicriviroc (VCV) is a new CCR5 antagonist with activity against human immunodeficiency virus type 1. Tsibris et al. (p. 8210-8214) studied 29 subjects with virologic failure from a clinical study of VCV and identified 1 individual infected with HIV-1 subtype C who developed VCV resistance. Experiments using viruses with chimeric envelopes demonstrated that changes within the V3 loop are sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences re-emerged following VCV discontinuation, suggesting that VCV resistance has associated fitness costs.
Journal of Virology, August 2008, p. 7757, Vol. 82, No. 16
0022-538X/08/$08.00+0 doi:10.1128/JVI.01265-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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