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Journal of Virology, June 2007, p. 6163, Vol. 81, No. 12
0022-538X/07/$08.00+0     doi:10.1128/JVI.00833-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Donaldson et al. (p. 6356-6368) combine extensive site-directed mutagenesis and recent crystal structures of the coronavirus replicase, nsp10, to identify regions that likely regulate viral RNA transcription and replication and ORF1a replicase protein processing. Genetic data demonstrate that nsp10 plays a critical role in virus replication, which depends on conservation of a central structural core and two zinc-binding fingers. The results challenge the biological relevance of nsp10 dodecameric structure in coronavirus replication.

Human Immunodeficiency Virus Type 1 Release Promoted by ALIX

Human immunodeficiency virus type 1 (HIV-1) Gag interacts with the endosomal sorting protein Tsg101 to allow release of progeny virions from the cell surface. Usami et al. (p. 6614-6622) now show that ALIX, another endosomal sorting protein that binds to HIV-1 Gag, can fully replace Tsg101. The activity of ALIX in HIV-1 release is dependent on its interaction with CHMP4, which functions downstream of both ALIX and Tsg101. The results demonstrate that ALIX has a dramatic effect on HIV-1 release if expressed at sufficiently high levels.

Productive Varicella-Zoster Virus Infection of Cultured Intact Human Ganglia

Varicella-zoster virus (VZV) is a neurotropic human herpesvirus that infects sensory ganglia. However, its exquisite species specificity has complicated development of experimental models that mimic productive infection of ganglionic cells. Gowrishankar et al. (p. 6752-6756) have developed an intact human dorsal root ganglia (DRG) explant model to show productive infection of neurons and nonneuronal cells. This system facilitates cell-free release of infectious virus from infected DRG, which differs from the highly cell-associated nature of VZV in other tissue-culture systems. This study establishes a new model for investigating VZV neurotropism and the relationship of VZV with human ganglionic cells in the context of the intact DRG.

Oncogenic Papillomaviruses in Macaques

Development of therapies for papillomavirus-associated neoplasia has been limited by the lack of a suitable animal model. In this study, Wood et al. (p. 6339-6345) identify in female cynomolgus macaques naturally occurring papillomaviruses associated with cervical intraepithelial neoplasia. The most common type of papillomavirus, called RhPV-d, is closely related phylogenetically to high-risk genital human papillomaviruses, experimentally transmissible between animals, and capable of inducing early cervical neoplasia. This work indicates that macaque genital papillomaviruses may provide an important model system for studying viral persistence, oncogenesis, and therapeutic interventions against cervical neoplasia.

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