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SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Coronaviruses encode a distant homolog of cellular exoribonucleases in the N-terminal half of nonstructural protein (nsp) 14, a protein distinct from the RNA-dependent RNA polymerase. However, the role of this nsp14 domain in viral replication is unclear. Eckerle et al. (p. 12135-12144) show that substitution of ExoN active-site residues in murine hepatitis virus results in viruses with a 15-fold increase in neutral mutations. These findings indicate that nsp14-ExoN functions in the prevention or repair of nucleotide incorporation errors and raise the possibility that nsp14 mediates RNA proofreading during genome replication.

Norwalk Virus RNA Is Infectious in Mammalian Cells

The study of human noroviruses has been hampered by the absence of a robust cell culture system. Guix et al. (p. 12238-12248) now show that transfection of Norwalk virus (NV) RNA isolated from human stools is fully infectious in cultured cells, leading to a single cycle of replication and release of viral particles. Overexpression of histo-blood group antigens, regarded as potential receptors for NV, enhances virus binding to cells but is not sufficient to allow a second round of viral replication. These results indicate that the block to NV infection in vitro occurs at the stage of receptor or coreceptor binding, entry, or uncoating.

Autophagy Control Is Dispensable for Herpes Simplex Virus Type 1 Replication

Autophagy, a cellular degradative pathway, is a host response to infection induced by a number of intracellular pathogens. The herpes simplex virus type 1 (HSV-1)-encoded virulence protein ICP34.5 counteracts both PKR-dependent translation inhibition and induction of autophagy. While the counteraction of autophagy is a critical determinant of neurovirulence, its role in promoting viral growth is unknown. Alexander et al. (p. 12128-12134) show that the prevention of translational arrest rather than control of autophagy is the dominant function of ICP34.5 in cell culture.

HPV Oncoproteins Alter Cytoskeletal Dynamics by Targeting p53

Cervical cancers express the E6 and E7 oncoproteins of particular human papillomavirus (HPV) types and thereby alter the host cell cytoskeleton. Cooper et al. (p. 12675-12679) demonstrate that E6 augments the kinetics of keratinocyte cell spreading by targeting the degradation of the p53 tumor suppressor. The targeted degradation of p53 by E6 may contribute to the invasive phenotype of cervical cells that contain high-risk strains of HPV.

Oseltamivir-Resistant H5N1 Influenza Viruses Are Not Compromised In Vitro or In Vivo

Effective antiviral drugs are essential for early control of an influenza pandemic, but the emergence of drug-resistant variants can complicate clinical management of infection. Yen et al. (p. 12418-12426) generated recombinant H5N1 influenza viruses containing wild-type neuraminidase (NA) or NA proteins with a single-amino-acid change at residue 274 or 294, which has been observed for persons who are infected with H5N1 viruses and who have been treated with oseltamivir. The results show that oseltamivir-resistant variants of H5N1 subtype are not altered in replication and exhibit high pathogenicity in mammals.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content