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Journal of Virology, October 2008, p. 9807, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01776-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

The polyomavirus and papillomavirus capsid subunits (capsomeres) are transported into the nucleus to the site of virion assembly via the cellular karyopherin transport pathway. Bird et al. (p. 9848-9857) show that binding of karyopherins to the viral capsid proteins affects their binding to DNA and inhibits their in vitro self-assembly into capsids. This work suggests that cellular karyopherins may have a chaperone function in DNA virus assembly by preventing protein interactions and premature assembly until the karyopherins are released from the coat protein subunits upon nuclear entry.

Influenza Virus Assembly Requires M1 and M2 Protein Interactions

The long cytoplasmic tail of the influenza A virus M2 proton-selective ion channel is largely dispensable for ion channel activity. However, Chen et al. (p. 10059-10070) show by mutational analysis and recovery of mutant virus that a specific region of the M2 cytoplasmic tail is required for efficient virus budding. Immunogold labeling of M1 and M2 on planar sheets of membrane from wild-type and mutant virus-infected cells suggests that a direct interaction between the cytoplasmic tail of M2 and M1 promotes efficient virus assembly.

Varicella-Zoster Virus ORF23 Plays a Key Role in Capsid Assembly and Skin Infection

Varicella-zoster virus (VZV) ORF23 encodes a conserved capsid protein, designated VP26 (UL35) in other alphaherpesviruses. Chaudhuri et al. (p. 10231-10246) find that in contrast to VP26, ORF23 has intrinsic nuclear localization capacity and is imported into the nucleus when coexpressed with major capsid protein ORF40. Whereas ORF23 is dispensable in vitro, it is essential for VZV lesion formation in human skin xenografts in the SCIDhu mouse model in vivo. Collectively, these findings suggest a model of capsid assembly in which ORF23 is required for nuclear translocation of the major capsid protein and associated proteins during VZV replication in human epidermal cells.

Polyfunctional T Cells Are the Key to Combating Hepatitis C Virus Infection

Alpha interferon therapy for hepatitis C is most successful when initiated early in the disease course, but the underlying mechanisms are unknown. Badr et al. (p. 10017-10031) demonstrate that early therapy can reconstitute virus-specific polyfunctional CD8⁺ memory T cells that are phenotypically and functionally identical to memory T cells generated during spontaneously resolved infections. These findings underscore the importance of early diagnosis and treatment of hepatitis C and suggest that characterization of virus-specific T cells based on several parameters rather than a single marker is predictive of the outcome of acute infection and therapy.

New Insights into Mechanisms of Scrapie-Induced Defects in Learning and Memory

The pathogenesis of scrapie-associated neurologic disease is unknown. Trifilo et al. (p. 9890-9899) find that scrapie infection of mice expressing a prion protein (PrP) without its glycophosphatidylinositol (GPI) membrane anchor leads to abundant accumulation of the abnormally folded disease-associated PrP, yet these mice live normal life spans (>600 days). In contrast, infection of mice expressing GPI-anchored PrP die (160 days) due to a chronic progressive neurodegenerative disease. However, GPI-anchorless PrP-infected mice suffer from defects in learning, memory, long-term potentiation, and neuronal excitability. This dysfunction increases over time and results from an increase in gamma aminobutyric acid (GABA) inhibition. Thus, the learning and memory defects in prion diseases may involve the GABA-ergic pathway.

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