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Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA

Abstract (if available)

Abstract All viruses need to interact with cellular complexes to escape host immune response and keep their infection persistent and tumorigenic. Kaposi's sarcoma‐associated herpesvirus (KSHV) encodes a viral Bcl-2 protein (kBcl2) critical for KSHV immune evasion of host defense. Up to now, two distinct functions—anti‐apoptosis and anti‐autophagy—have been identified of kBcl2 in viral lifecycle. A recent study showed that kBcl-2 is critically required for the lytic replication of KSHV, which is surprisingly independent of kBcl-2's anti‐apoptosis and anti‐autophagy activities. Moreover, residue E14 of kBcl-2 has been shown to be essential for viral replication in that mutation of residue E14 to alanine (E14A) abolishes the ability of kBcl-2 in promoting viral replication. However, the molecular mechanism by which kBcl-2 mediates viral progeny production remains unknown. Our recent study showed that NM23-H2 interacts with kBcl-2 and this interaction is negotiated by the E14 residue of kBcl-2. Moreover, kBcl-2 colocalizes with NM23-H2 at the ER, and a depletion of NM23-H2 impairs viral lytic replication. Thus, we postulate that kBcl-2 regulation of host NM23-H2 represents a significant new mechanism required for viral lytic replication.