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Journal of Virology, June 2006, p. 5103, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00692-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Poliovirus protein 2C contains an N-terminal amphipathic helix that mediates association of the protein with membranes. Teterina et al. (p. 5327-5337) constructed a chimeric virus that substituted the orthologous amphipathic helix from human rhinovirus 14. The chimeric virus grew very poorly, but large-plaque variants emerged that contained compensating mutations in either the 2B or 3A sequence. Concordantly, these viral proteins were shown to directly interact. The results indicate a network of functional interactions among 2B, 2C, and 3A protein sequences in the induced membrane structures that form the viral RNA replication complex.

The Third Man: Intracellular Trafficking of the Arenavirus Envelope Glycoprotein

The arenavirus envelope glycoprotein (GP-C) is unusual in that the mature complex retains the cleaved, 58-amino-acid signal peptide (SSP) as a third subunit. Agnihothram et al. (p. 5189-5198) show that SSP association in the GP-C complex of Junìn virus overcomes specific retention signals in the cytoplasmic domain of the G2 transmembrane subunit, thereby allowing GP-C transit from the endoplasmic reticulum and through the Golgi for proteolytic maturation. This quality-control mechanism ensures that only the fully assembled complex is transported to the cell surface for virion assembly.

Charged Residues Potentiate TRIM5 Antiviral Activity

TRIM5 is a primate protein that restricts infection by particular retroviruses. Although human TRIM5 potently blocks N-tropic murine leukemia virus (N-MLV) infection, monkey TRIM5 is less active. Perron et al. (p. 5631-5636) show that the potency determinants reside in two regions of the TRIM5 B30.2 domain that are predicted to be surface-exposed loops. Negatively charged residues in TRIM5 appear to complement a positively charged residue on the targeted retroviral capsid. This work assists our understanding of how TRIM5 proteins recognize particular retroviruses.

Herpes Simplex Virus and MicroRNAs

MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression in higher eukaryotes. Previously, no alphaherpesvirus had been shown to encode and express miRNAs. Cui et al. (p. 5499-5508) used a computational approach to predict miRNAs encoded by herpes simplex virus 1 (HSV-1) and then verified the expression of at least one of these, which is encoded upstream of the latency-associated transcript. The findings suggest that HSV-1 miRNAs may regulate viral and host gene expression.

VP24 is an Ebola Virus-Encoded Inhibitor of Interferon-Signaling

Ebola virus (EBOV) infection blocks both cellular production of alpha/beta interferon (IFN-/ß) and cellular responses to IFN/ß and IFN. While EBOV VP35 was previously identified as an EBOV-encoded inhibitor of IFN/ß production, Reid et al. (p. 5156-5167) now provide evidence that the EBOV VP24 protein can inhibit cellular responses to IFN/ß and IFN. This inhibition correlates with the capacity of VP24 to inhibit a key step in IFN signaling pathways, the nuclear accumulation of activated STAT1. Inhibitors that target this novel function of VP24 may enhance the efficacy of IFNs as anti-EBOV therapeutics.

CNS Expression of Innate Immune Response Genes Induced by High Doses of Adenoviral Vectors

Adenoviral vectors (Adv) injected into the brain induce expression of interferon-regulated genes and chemokine genes. These responses are only seen following injection of 1 x 10⁸ IU but do not occur at lower vector doses. Adv doses below this threshold do not cause a significant increase in proinflammatory gene expression and provide long-term transgene expression; the reverse is true of higher doses. Zirger et al. (p. 5655-5659) establish an upper limit for noninflammatory Adv doses per brain injection site that provide long-term transgene expression. The existence of this inflammatory threshold indicates that powerful promoters must be used to achieve therapeutically relevant gene transfer at noninflammatory vector doses.

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