Identification of the in vivo role of a viral bcl-2

The Journal of Experimental Medicine
Shivaprakash GangappaHerbert W Virgin

Abstract

Many gamma-herpesviruses encode candidate oncogenes including homologues of host bcl-2 and cyclin proteins (v-bcl-2, v-cyclin), but the physiologic roles of these genes during infection are not known. We show for the first time in any virus system the physiologic role of v-bcl-2. A gamma-herpesvirus v-bcl-2 was essential for efficient ex vivo reactivation from latent infection, and for both persistent replication and virulence during chronic infection of immunocompromised (interferon [IFN]-gamma(-/-)) mice. The v-cyclin was also critical for the same stages in pathogenesis. Strikingly, while the v-bcl-2 and v-cyclin were important for chronic infection, these genes were not essential for viral replication in cell culture, viral replication during acute infection in vivo, establishment of latent infection, or virulence during acute infection. We conclude that v-bcl-2 and v-cyclin have important roles during latent and persistent gamma-herpesvirus infection and that herpesviruses encode genes with specific roles during chronic infection and disease, but not acute infection and disease. As gamma-herpesviruses primarily cause human disease during chronic infection, these chronic disease genes may be important targets for therapeuti...Continue Reading

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Citations

Jan 14, 2009·Applied Microbiology and Biotechnology·Sandra JuanolaFrancesc Gòdia
Sep 23, 2003·Journal of Molecular Biology·Qiulong HuangEdward T Olejniczak
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Nov 6, 2007·Journal of Virology·Vera L TarakanovaHerbert W Virgin
Oct 22, 2002·Journal of Virology·Shivaprakash GangappaHerbert W Virgin
Jun 14, 2003·Journal of Virology·Sofia MarquesJ Pedro Simas
Jan 29, 2003·Journal of Virology·Scott A TibbettsHerbert W Virgin
Apr 15, 2003·Journal of Virology·Linda F van DykSamuel H Speck
Jun 15, 2004·Journal of Virology·Rebecca L Sparks-ThissenHerbert W Virgin
Oct 28, 2004·Journal of Virology·Joy LohHerbert W Virgin
Jul 5, 2005·Journal of Virology·Nina SantiØystein Evensen
Feb 1, 2005·Journal of Virology·Douglas C BraatenHerbert W Virgin
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Jun 3, 2008·PLoS Pathogens·Lorenzo GalluzziGuido Kroemer
Apr 5, 2008·PLoS Pathogens·Andrea M SiegelSamuel H Speck

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Methods Mentioned

BETA
PCR
transfection
lavage
transgenic

Software Mentioned

GraphPad
GraphPad Prism

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