Epstein-Barr virus suppresses N⁶-methyladenosine modification of TLR9 to promote immune evasion.

ABSTRACT: Epstein-Barr virus (EBV) is a human tumor virus associated with a variety of malignancies, including nasopharyngeal carcinoma, gastric cancers, and B-cell lymphomas. N⁶-methyladenosine (m⁶A) modifications modulate a wide range of cellular processes and participate in the regulation of virus-host cell interactions. Here, we discovered that EBV infection downregulates toll-like receptor 9 (TLR9) m⁶A modification levels and thus inhibits TLR9 expression. TLR9 has multiple m⁶A modification sites. Knockdown of METTL3, an m⁶A "writer", decreases TLR9 protein expression by inhibiting its mRNA stability. Mechanistically, Epstein-Barr nuclear antigen 1 increases METTL3 protein degradation via K48-linked ubiquitin-proteasome pathway. Additionall

SUBMITTER: Zhang X 

PROVIDER: S-EPMC11061751 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature