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Journal of Virology, October 2007, p. 10207-10208, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.01719-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Ebola virus, severe acute respiratory syndrome coronavirus, Hendra virus, Nipah virus, and murine hepatitis virus infect cells via a membrane fusion event that is triggered by low pH and involves cleavage of the viral fusion proteins by an endosomal protease of the cathepsin family. Kumar et al. (p. 10506-10514) provide intriguing new evidence that the fusion event for a murine retrovirus also involves cathepsin cleavage of the viral envelope glycoprotein. However, membrane fusion is triggered by receptor binding, not by low pH, for this retrovirus. It is now evident that cathepsin-mediated activation of viral membrane fusion is not limited to the acid-triggered viral fusion proteins.

Insights into the Determinants of Hepatitis C Virus Core Protein Function

Hepatitis C virus (HCV) has recently been propagated in tissue culture, enabling studies of its assembly. Murray et al. (p. 10220-10231) show that the HCV core protein is essential for infectious virus production and that, unlike the related flavivirus capsid protein, it is highly sensitive to mutation. For several core mutants, defects early in infectious particle assembly could be overcome by compensatory mutations in the nonstructural proteins. These findings provide a first look at the determinants of core protein function in HCV virion production and suggest a close interplay between structural and nonstructural proteins during HCV morphogenesis.

Alphavirus Replicase Protein Traffics between the Cytoplasm and Nucleus

The multifunctional replicase protein nsP2 of a New World alphavirus, Venezuelan equine encephalitis virus, plays a key role in viral replication. Montgomery and Johnston (p. 10268-10279) demonstrate that nsP2 cycles into and out of the nucleus by using specific nuclear import and export signals. Mutations disrupting the normal localization of nsP2 compromise virus viability. This work suggests that nuclear/cytoplasmic cycling of nsP2 is necessary for alphavirus replication, perhaps because it inhibits nuclear transport of critical cellular factors required for the activation of host defense mechanisms.

Epstein-Barr Virus Nuclear Antigens Induce Metastasis in a Mouse Model

Epstein-Barr virus (EBV) nuclear antigens EBNA1 and EBNA3C serve important functions in maintenance of the EBV genome and regulation of transcription, respectively. Kaul et al. (p. 10352-10361) show that the interaction of EBNA1 and EBNA3C with cellular protein Nm23-H1 promotes cell migration and metastasis of cancer cells in vivo. The EBV proteins promote the growth of transformed cells in vivo, but their expression is less critical during later stages of tumor development. The EBV proteins also enhance the capacity of the cancer cells to metastasize to the lungs in nude mice. These findings bridge the expression of the EBV nuclear proteins with tumorigenesis and metastasis and provide new ideas for targeting EBV-associated human cancers.

The Mx1 Gene Protects Mice against Highly Lethal Human Influenza Viruses

Mice carrying a wild-type Mx1 gene differ from standard laboratory mice in that they are highly resistant to infection with common laboratory strains of influenza A virus. Tumpey et al. (p. 10818-10821) now report that Mx1 also protects mice against the pandemic human 1918 influenza virus and a highly lethal human H5N1 strain from Vietnam. Resistance to H5N1 was greatly enhanced if the animals were treated with a single dose of exogenous alpha interferon before infection. Thus, interferon-induced Mx1 expression represents a key component of the murine innate immune system that mediates protection against epidemic and pandemic influenza viruses.

Measles Virus as a Divalent Vaccine Vector

The live-attenuated measles virus vaccine has an outstanding record of safety and efficacy. Reyes del Valle et al. (p. 10597-10605) now show that the measles vaccine strain also can deliver a foreign antigen while retaining measles vaccine function in macaques. Unexpectedly, small differences in foreign antigen (HBsAg) expression levels induced vastly different antibody levels in two animal species. The threshold of expression eliciting a strong humoral response was lower in mice than in macaques. These studies suggest that vectored measles viruses have utility as multivalent vaccines.

Antiprion Drugs Cure Cells by Reversing Proteasome Inhibition

Congo red derivatives inhibit prion-infected cells from expressing PrP^Sc. Webb et al. (p. 10729-10741) show that these derivatives cure the same cells of the infectious agent of prion disease. Although Congo red derivatives interact with the aggregated proteins that form prions and possess antioxidant-like activity, the derivatives capable of curing cells do so by increasing the cellular capacity to degrade the abnormal protein. These results suggest that targeting the activity of the proteasome may lead to a cure for prion disease.

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