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Journal of Virology, November 2007, p. 11553, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01962-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Astroviruses are a leading cause of viral diarrhea in young children. To understand mechanisms by which astroviruses induce diarrhea, Moser et al. (p. 11937-11945) examined the effect of astrovirus infection on intestinal barrier permeability, an in vitro predictor of diarrhea. Astroviruses increased permeability in polarized cells and decreased barrier function, which was associated with disruption of occludin and the actin cytoskeleton. UV-inactivated virus and recombinant virus-like particles also increased barrier permeability. These results suggest that astrovirus structural proteins elicit pathological effects.

Human Cytomegalovirus Turns the Cell Outside-In

Human cytomegalovirus induces profound changes in infected-cell morphology, including formation of large cytoplasmic inclusions that correspond to the virion assembly complex (AC). However, details of AC structure have been lacking. Das et al. (p. 11861-11869) show that the AC is arranged such that Golgi- and trans-Golgi-derived vesicles are at the outer periphery of the AC and early endosome-derived vesicles are at its center. This counterintuitive arrangement nonetheless allows for a conventional order of membrane-protein biosynthesis and transport. The resulting model of AC structure suggests a mechanism by which the virus can regulate the order of tegument assembly.

Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1

Viruses must evade potent antiviral interferon responses to replicate efficiently. Wathelet et al. (p. 11620-11633) show that the severe acute respiratory syndrome coronavirus (SARS-CoV) inhibits both virus- and interferon-dependent signaling while being sensitive to the interferon-induced antiviral state. Expression of nsp1 in isolation recapitulated the signaling inhibition observed in infected cells. SARS-CoV with a mutation in nsp1 replicated as efficiently as wild-type virus in cells with a defective interferon response but was strongly attenuated in interferon-sensitive cells. This work identifies nsp1 as a virulence factor that may contribute to pathogenicity by inhibiting antiviral signaling, thus favoring viral replication.

Cytotoxic T-Cell Epitope Ontogeny versus Major Histocompatibility Complex Class I Downregulation in Simian Immunodeficiency Virus-Infected Cells

Nef-mediated major histocompatibility complex class I (MHC-I) downregulation shields human immunodeficiency virus (HIV)-infected cells from cytotoxic T-cell (CTL)-mediated lysis. Sacha et al. (p. 11703-11712) demonstrate that Nef begins to down-regulate MHC-I from the surface of infected cells at 12 h postinfection, concomitant with the presentation of Nef-derived CTL epitopes. Surprisingly, Pol-specific CTLs recognize virion-derived Pol epitopes on the surface of infected cells as early as 2 h postinfection, well before MHC-I downregulation. Therefore, Pol-specific CTLs may be more effective in the clearance of HIV-infected cells than previously thought.

Cytokine Teamwork Matters

CD4⁺ T-cell help is essential for the functioning of cytotoxic CD8⁺ T cells and B cells. Kannaganat et al. (p. 12071-12076) demonstrate that human immunodeficiency virus (HIV)-infected individuals with controlled infections maintain high levels of multicytokine-expressing CD4⁺ T cells that perform multiple functions. However, individuals with uncontrolled infections predominantly maintain single-cytokine-expressing CD4⁺ T cells that perform fewer functions. These results suggest that HIV vaccine strategies capable of eliciting multicytokine-expressing CD4⁺ T cells are more likely to be efficacious.

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