Viral Bcl-2 encoded by the Kaposi's sarcoma-associated herpesvirus is vital for virus reactivation

Anastasia Gelgor, Inna Kalt, Shir Bergson, Kevin F. Brulois, Jae U. Jung, Ronit Sarid

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 16 (orf16) encodes a viral Bcl-2 (vBcl-2) protein which shares sequence and functional homology with the Bcl-2 family. Like its cellular homologs, vBcl-2 protects various cell types from apoptosis and can also negatively regulate autophagy. vBcl-2 is transcribed during lytic infection; however, its exact function has not been determined to date. By using bacterial artificial chromosome 16 (BAC16) clone carrying the full-length KSHV genome, we have generated recombinant KSHV mutants that fail to express vBcl-2 or express mCherry-tagged vBcl-2. We show that the vBcl-2 protein is expressed at relatively low levels during lytic induction and that a lack of vBcl-2 largely reduces the efficiency of KSHV reactivation in terms of lytic gene expression, viral DNA replication, and production of infectious particles. In contrast, the establishment of latency was not affected by the absence of vBcl-2. Our findings suggest an important role for vBcl-2 during initial phases of lytic reactivation and/or during subsequent viral propagation. Given the known functions of vBcl-2 in regulating apoptosis and autophagy, which involve its direct interaction with cellular proteins and thus require high levels of protein expression, it appears that vBcl-2 may have additional regulatory functions that do not depend on high levels of protein expression.

Original languageEnglish
Pages (from-to)5298-5307
Number of pages10
JournalJournal of Virology
Volume89
Issue number10
DOIs
StatePublished - May 2015

Bibliographical note

Publisher Copyright:
© 2015, American Society for Microbiology.

Funding

FundersFunder number
National Institute of Allergy and Infectious DiseasesR01AI073099

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