Kaposi's sarcoma-associated herpesvirus (KSHV) utilizes the NDP52/CALCOCO2 selective autophagy receptor to disassemble processing bodies

Kaposi's sarcoma-associated herpesvirus (KSHV) causes the inflammatory and angiogenic endothelial cell neoplasm, Kaposi's sarcoma (KS). We previously demonstrated that the KSHV Kaposin B (KapB) protein promotes inflammation via the disassembly of cytoplasmic ribonucleoprotein granules call...

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Bibliographic Details
Published in:PLoS pathogens 2023-01, Vol.19 (1), p.e1011080-e1011080
Main Authors: Robinson, Carolyn-Ann, Singh, Gillian K, Kleer, Mariel, Katsademas, Thalia, Castle, Elizabeth L, Boudreau, Bre Q, Corcoran, Jennifer A
Format: Article
Language:English
Subjects:
Angiogenesis
Autophagy
Autophagy (Cytology)
Biology and Life Sciences
Causes of
Cell death
Chemical synthesis
Cytokines
Dismantling
Endothelial cells
Endothelial Cells - metabolism
Gene expression
Health aspects
Herpes viruses
Herpesviridae Infections - metabolism
Herpesvirus 8, Human - genetics
Herpesviruses
Homeostasis
Humans
Identification and classification
Infections
Inflammation
Interferon
Kaposi's sarcoma
Kaposis sarcoma
Kinases
Medicine and Health Sciences
Nuclear Proteins - metabolism
Phosphorylation
Physiological aspects
Processing Bodies
Proteins
Receptors
Research and Analysis Methods
Sarcoma
Sarcoma, Kaposi
Scaffolding
Viral infections
Viruses
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Summary:Kaposi's sarcoma-associated herpesvirus (KSHV) causes the inflammatory and angiogenic endothelial cell neoplasm, Kaposi's sarcoma (KS). We previously demonstrated that the KSHV Kaposin B (KapB) protein promotes inflammation via the disassembly of cytoplasmic ribonucleoprotein granules called processing bodies (PBs). PBs modify gene expression by silencing or degrading labile messenger RNAs (mRNAs), including many transcripts that encode inflammatory or angiogenic proteins associated with KS disease. Although our work implicated PB disassembly as one of the causes of inflammation during KSHV infection, the precise mechanism used by KapB to elicit PB disassembly was unclear. Here we reveal a new connection between the degradative process of autophagy and PB disassembly. We show that both latent KSHV infection and KapB expression enhanced autophagic flux via phosphorylation of the autophagy regulatory protein, Beclin. KapB was necessary for this effect, as infection with a recombinant virus that does not express the KapB protein did not induce Beclin phosphorylation or autophagic flux. Moreover, we showed that PB disassembly mediated by KSHV or KapB, depended on autophagy genes and the selective autophagy receptor NDP52/CALCOCO2 and that the PB scaffolding protein, Pat1b, co-immunoprecipitated with NDP52. These studies reveal a new role for autophagy and the selective autophagy receptor NDP52 in promoting PB turnover and the concomitant synthesis of inflammatory molecules during KSHV infection.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011080