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Journal of Virology, February 2007, p. 1541-1542, Vol. 81, No. 4
0022-538X/07/$08.00+0     doi:10.1128/JVI.02801-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Extinction of RNA viruses due to excess mutations (lethal mutagenesis) may select mutant polymerases refractory to the incorporation of mutagenic nucleotide analogues. Sierra et al. (p. 2012-2024) report the selection of a new foot-and-mouth disease virus (FMDV) mutant with decreased sensitivity to ribavirin. The new mutation enhances viral fitness in the presence of ribavirin and diminishes incorporation of the mutagen. These findings suggest that picornavirus polymerases may contain multiple sites related to template copying fidelity that modulate incorporation of nucleotide analogues. Thus, it is possible that selection of such mutants will jeopardize lethal mutagenesis.

Papillomavirus E2 Binds Mitosis-Specific Kinesin MKlp2

Papillomavirus E2 is a sequence-specific DNA-binding protein required for partitioning viral episomes during mitosis. Although the mechanism is unknown, two cellular factors, Brd4 and ChlR1, are involved in viral segregation. Yu et al. (p. 1736-1745) provide evidence that E2 and viral genomes are in complex with mitotic kinesin-like protein 2 (MKlp2). These results suggest involvement of a mitosis-specific motor protein in partitioning viral genomes.

Two Human Immunodeficiency Virus Type 1 Particles Can Activate Signaling in Resting T Cells

Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) binding to viral entry receptors induces cell signaling. The relevance of such signaling in HIV-1 replication is controversial because of the excess Env concentrations used in previous studies. Melar et al. (p. 1773-1785) used intracellular Ca₂⁺ changes as a signaling marker to study responses of individual T cells to low-level Env binding. Env-mediated Ca₂⁺ flux is coreceptor-mediated, coreceptor-specific, CD4-dependent, and potent only when Env is virion-bound. Importantly, the binding of just two HIV-1 particles will elicit a T-cell response, indicating that this signaling is likely to be relevant in vivo.

Kinomic Analysis of Mild and Lethal Arenavirus Infection

Phosphorylation events are key regulators of cell signaling. Methods to study these changes globally have lagged behind techniques for genomic and proteomic analyses. Bowick et al. (p. 1923-1933) used two variants of Pichinde virus, which cause either mild or lethal disease, respectively, and a high-throughput kinase assay to investigate the phosphorylation changes induced by these infections. The results indicate that the mild variant is associated with a broad host response, while the lethal variant leads to suppression. These findings suggest new determinants of the protective immune response elicited by Pichinde virus and perhaps other arenaviruses.

Costimulatory Signals Transduced through CD2 Can Reactivate Latent Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1

The latent reservoir for human immunodeficiency virus type 1 (HIV-1) in resting CD4⁺ T cells poses a barrier to HIV-1 eradication with antiretroviral drugs. Shen et al. (p. 1660-1670) employ a simian immunodeficiency virus (SIV)-macaque model to study pathways for the reactivation of latent SIV and HIV-1. Coculture of infected resting macaque CD4⁺ T cells with certain human lymphoid cell lines activates the macaque T cells and the latent SIV they carry in a process dependent on CD2 but not the T-cell receptor (TCR). The finding that costimulatory signals can induce reactivation of latent virus without TCR engagement reveals a new pathway to target latent HIV-1.

How Murine MusD LTR-Retrotransposons Arose from the "Intracellularization" of an Ancient Retrovirus during Evolution

MusD LTR-retrotransposons active for transposition are closely related to betaretroviruses but lack an envelope gene. Ribet et al. (p. 1888-1898) show that these elements encode strictly intracellular virus-like particles. The intracytoplasmic distribution of these particles is strictly dependent on a defect in the plasma membrane targeting signal of the Gag protein, precluding viral particle release. This sequestration is associated with increased retrotransposition efficiency. Collectively, these findings suggest a molecular pathway for the evolution of an ancestral infectious retrovirus to a successful "intracellularized" insertional mutagen.

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