Related Experiment Video
Updated: Oct 1, 2026
Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
Identification of the in vivo role of a viral bcl-2
Shivaprakash Gangappa1, Linda F van Dyk, Travis J Jewett
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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 therapeutic intervention.
Insights
Gamma-herpesviruses
Area of Science:
- Virology
- Oncology
- Immunology
Background:
- Gamma-herpesviruses encode proteins similar to host bcl-2 and cyclin.
- The physiological roles of these viral (v) genes during infection remain largely unknown.
- Understanding these roles is crucial for developing antiviral therapies.
Purpose of the Study:
- To elucidate the physiological roles of viral bcl-2 (v-bcl-2) and viral cyclin (v-cyclin) in gamma-herpesvirus infection.
- To determine the importance of these genes in viral reactivation, replication, and pathogenesis.
- To investigate the differential roles of v-bcl-2 and v-cyclin in acute versus chronic infection.
Main Methods:
- Utilizing a gamma-herpesvirus model system.
- Assessing viral reactivation ex vivo.
- Evaluating viral replication and virulence in immunocompromised (interferon [IFN]-gamma(-/-)) mice during acute and chronic infections.
- Comparing gene essentiality in cell culture versus in vivo models.
Main Results:
- Viral bcl-2 (v-bcl-2) is essential for efficient ex vivo reactivation from latency.
- v-bcl-2 and v-cyclin are critical for persistent replication and virulence during chronic infection in IFN-gamma(-/-) mice.
- These viral genes are not essential for viral replication in cell culture, acute infection, or establishment of latency.
- v-bcl-2 and v-cyclin play specific roles in chronic gamma-herpesvirus pathogenesis.
Conclusions:
- v-bcl-2 and v-cyclin are key regulators of latent and persistent gamma-herpesvirus infections.
- Herpesviruses encode specific genes for chronic disease, distinct from those required for acute infection.
- These chronic disease-associated genes represent potential therapeutic targets for human diseases caused by gamma-herpesviruses.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:51Mechanisms of Retrovirus-induced Cancers
01:51Mechanisms of Retrovirus-induced Cancers