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KSHV Manipulation of Antigen Presentation via the Ubiquitin Proteasome System
Author(s) -
Causey Amerria M.,
Ehrlich Elana S.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r4900
Subject(s) - lytic cycle , ubiquitin ligase , ubiquitin , antigen presentation , biology , proteasome , kaposi's sarcoma associated herpesvirus , microbiology and biotechnology , antigen , antigen processing , immune system , virology , gene , virus , immunology , genetics , t cell , herpesviridae , viral disease
Kaposi Sarcoma‐associated herpesvirus (KSHV, HHV‐8) is a human oncovirus with a two‐stage life cycle consisting of latent and lytic replication. Lytic replication is characterized by the expression of late genes, the assembly of viral particles, and is initiated by the expression of RTA. In addition to being a transcription factor, RTA is an E3 ubiquitin ligase with the ability to target proteins for degradation via the ubiquitin‐proteasome system (UPS). Previously in our lab, through a comparative proteomics study, we identified proteins that displayed increased ubiquitination in the presence of RTA. Three proteins identified are known to be involved in the process of antigen presentation. We hypothesize KSHV RTA is targeting these proteins to maintain a persistent infection. Here we provide preliminary evidence that suggests that RTA targets the process of antigen processing and presentation. suggesting a novel mechanism for evasion of the immune response by KSHV RTA. We demonstrate degradation of HLA, PSMB3, and TAP2 cells expressing RTA. Cells expressing RTA exhibited decreased peptide loading on HLA. Our data suggests a novel mechanism for evasion of the host immune response by KSHV RTA.