title: 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.
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.
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kwun
authors.forename: Suzane Ramos
authors.initials: SR
authors.lastname: da Silva
authors.forename: Huilian
authors.initials: H
authors.lastname: Qin
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
authors.forename: Rusung
authors.initials: R
authors.lastname: Tan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Moore
mesh_terms: D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D019288:Herpesvirus 8, Human / Q000276:immunology* / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism; D017384:Sequence Deletion; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D009687:Nuclear Proteins; D037521:Virulence Factors; C109540:latency-associated nuclear antigen