Kaposi's Sarcoma-Associated Herpesvirus K7 Modulates Rubicon-Mediated Inhibition of Autophagosome Maturation

Abstract

bAutophagy is an important innate safeguard mechanism for protecting an organism against invasion by pathogens. We have previously discovered that Kaposi's sarcoma-associated herpesvirus (KSHV) evades this host defense through tight suppression of autophagy by targeting multiple steps of autophagy signal transduction. Here, we report that KSHV K7 protein interacts with Rubicon autophagy protein and inhibits the autophagosome maturation step by blocking Vps34 enzymatic activity, further highlighting how KSHV deregulates autophagy-mediated host immunity for its life cycle.

Epstein-Barr Virus Blocks the Autophagic Flux and Appropriates the Autophagic Machinery To Enhance Viral Replication

“…Regarding the relationship between autophagy and viral replication, it has been demonstrated that several viruses, such as HCV (42) and HBV, stimulate an incomplete autophagy (43) and that autophagy is involved in KSHV replication (15). However, a KSHV protein, K7, expressed during its lytic phase, is able to block the autophagic process (44). Regarding EBV proteins, it is known that the latent membrane protein 1 (LMP1) regulates autophagy to control its own degradation (45).…”

Identification of the Essential Role of Viral Bcl-2 for Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication

“…Specifically, autophagy combats and defends infected cells by enhancing the degradation of intracellular pathogens (6,7). On the other hand, to avoid the host's autophagymediated immune responses, herpesviruses have evolved elaborate mechanisms to block different aspects of the autophagy pathway for their persistent infection (8)(9)(10). To overcome cellular autophagy, KSHV has evolved several viral gene products to modulate different steps of autophagy signaling (8,9,11,12).…”

“…On the other hand, to avoid the host's autophagymediated immune responses, herpesviruses have evolved elaborate mechanisms to block different aspects of the autophagy pathway for their persistent infection (8-10). To overcome cellular autophagy, KSHV has evolved several viral gene products to modulate different steps of autophagy signaling (8,9,11,12). For Citation Liang Q, Chang B, Lee P, Brulois KF, Ge J, Shi M, Rodgers MA, Feng P, Oh B-H, Liang C, Jung JU.…”

“…On the other hand, to avoid the host's autophagymediated immune responses, herpesviruses have evolved elaborate mechanisms to block different aspects of the autophagy pathway for their persistent infection (8)(9)(10). To overcome cellular autophagy, KSHV has evolved several viral gene products to modulate different steps of autophagy signaling (8,9,11,12). For instance, viral Bcl-2 (vBcl-2) interacts with the Beclin-1 complex to downregulate autophagy at the vesicle nucleation step (11), viral FLIP (vFLIP) suppresses autophagy at the vesicle elongation step by preventing the Atg3 E2 enzyme from binding and processing light chain 3 (LC3) (12), and K7 interacts with autophagy inhibitor Rubicon to impair the autophagosome maturation step (9).…”

“…To overcome cellular autophagy, KSHV has evolved several viral gene products to modulate different steps of autophagy signaling (8,9,11,12). For instance, viral Bcl-2 (vBcl-2) interacts with the Beclin-1 complex to downregulate autophagy at the vesicle nucleation step (11), viral FLIP (vFLIP) suppresses autophagy at the vesicle elongation step by preventing the Atg3 E2 enzyme from binding and processing light chain 3 (LC3) (12), and K7 interacts with autophagy inhibitor Rubicon to impair the autophagosome maturation step (9). These pieces of evidence further underscore the importance of autophagy as the host's critical immune control.…”