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

Journal Article · Sun Apr 10 00:00:00 EDT 2011 · Virology

DOI:https://doi.org/10.1016/j.virol.2011.01.026· OSTI ID:21486930

Kwun, Hyun Jin ^[1]; Ramos da Silva, Suzane ^[1]; Huilian, Qin ^[2]; Ferris, Robert L ^[3]; Rusung, Tan ^[2]

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1. Cancer Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA (United States)
2. Department of Pathology and Laboratory Medicine, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia (Canada)
3. Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

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.

• OSTI ID: 21486930
• Journal Information: Virology, Vol. 412, Issue 2; Other Information: DOI: 10.1016/j.virol.2011.01.026; PII: S0042-6822(11)00040-7; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
• Country of Publication: United States
• Language: English

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60 APPLIED LIFE SCIENCES
ENDOPLASMIC RETICULUM
HISTOCOMPATIBILITY COMPLEX
LYMPHOCYTES
ONCOGENIC VIRUSES
PEPTIDES
SARCOMAS
TRANSLOCATION
ANIMAL CELLS
ANTIGENS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISEASES
LEUKOCYTES
MATERIALS
MICROORGANISMS
NEOPLASMS
ORGANIC COMPOUNDS
PARASITES
PROTEINS
SOMATIC CELLS
VIRUSES