The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation

• Published in: Virology (New York, N.Y.) N.Y.), 2011-04, Vol.412 (2), p.357-365
• Main Authors: Kwun, Hyun Jin, da Silva, Suzane Ramos, Qin, Huilian, Ferris, Robert L, Tan, Rusung, Chang, Yuan, Moore, Patrick S
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL CELLS; Antigen Presentation; ANTIGENS; Antigens, Viral - immunology; Antigens, Viral - metabolism; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CELL CONSTITUENTS; Cell Line; Cloning, Molecular; CONNECTIVE TISSUE CELLS; DISEASES; ENDOPLASMIC RETICULUM; Epstein-Barr virus; Herpesvirus 8, Human - immunology; Herpesvirus 8, Human - pathogenicity; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; HISTOCOMPATIBILITY COMPLEX; Human herpesvirus 8; Humans; Immune Evasion; Infectious Disease; Kaposi's sarcoma-associated herpesvirus; Latency-associated nuclear antigen 1; LEUKOCYTES; LYMPHOCYTES; Major histocompatibility complex class I; MATERIALS; MICROORGANISMS; NEOPLASMS; Nuclear Proteins - immunology; Nuclear Proteins - metabolism; ONCOGENIC VIRUSES; ORGANIC COMPOUNDS; PARASITES; PEPTIDES; PROTEINS; SARCOMAS; Sequence Deletion; SOMATIC CELLS; TRANSLOCATION; Virulence Factors - immunology; Virulence Factors - metabolism; VIRUSES
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2011.01.026

Abstract KSHV LANA1, a latent protein expressed during chronic infection to maintain a viral genome, inhibits major histocompatibility complex class I (MHC I) 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.