期刊
VIROLOGY
卷 412, 期 2, 页码 357-365出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.01.026
关键词
Kaposi's sarcoma-associated herpesvirus; Latency-associated nuclear antigen 1; Major histocompatibility complex class I; Immune evasion
类别
资金
- NIH [NCI121930]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [BEX1049/05-4]
- American Cancer Society
- UPCI Core Facility Cancer Center [P30 CA047904]
KSHV LANA1, a latent protein expressed during chronic infection to maintain a viral genome, inhibits major histocompatibility complex class I (MHCI) peptide presentation in cis as a means of immune evasion. Through deletional cloning, we localized this function to the LANA1 central repeat 1 (CR1) subregion. Other CR subregions retard LANA1 translation and proteasomal processing but do not markedly inhibit LANA1 peptide processing by MHC I. Inhibition of proteasomal processing ablates LANA1 peptide presentation. Direct expression of LANA1 within the endoplasmic reticulum (ER) overcomes CR1 inhibition suggesting that CR1 acts prior to translocation of cytoplasmic peptides into the ER. By physically separating CR1 from other subdomains, we show that LANA1 evades MHC I peptide processing by a mechanism distinct from other herpesviruses including Epstein-Barr virus (EBV). Although LANA1 and EBV EBNA1 are functionally similar, they appear to use different mechanisms to evade host cytotoxic T lymphocyte surveillance. (C) 2011 Elsevier Inc. All rights reserved.
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