In cis inhibition of antigen processing by the latency-associated nuclear antigen I of Kaposi sarcoma herpes virus.
Kaposi sarcoma Herpes virus (KSHV), also known as human Herpes virus 8 (HHV8), can persist as episome in target cells. The latency-associated nuclear antigen 1 (LANA-1) is a key component of the latency process, and may be a functional equivalent of the EBNA-1 protein of Epstein-Barr virus. EBNA-1 can subdue immune recognition by virtue of a long glycine and alanine-rich repeat, which interferes with the proteasomal degradation of EBNA-1 and in this way averts the presentation of antigenic peptides derived from it. LANA-1 contains a strongly acidic-repeat region of approximately 580 amino acids, which consists almost exclusively of aspartic acid, glutamine, and glutamic acid residues. The LANA-1 repeat is not similar to the EBNA-1 Gly-Ala-rich repeat. We demonstrate that this acidic region could inhibit antigen processing in cis. Upon transfection of expression vectors containing LANA-1-eGFP fusion genes the cells did not present an ovalbumin-derived H2K(b)-restricted CTL epitope inserted at the carboxyl terminus of the GFP reporter. Deletion of the central acidic-repeat region of LANA-1 abolished the capacity of LANA-1 to block antigen presentation. Similar to the EBNA-1-derived Gly-Ala-rich repeat, the LANA-1 repeat does not inhibit presentation in trans: co-transfection of LANA-1 expression vectors does not inhibit presentation of the ova epitope from the GFP(Ova) fusion protein. These data demonstrate for the first time that the acidic-repeat region of LANA-1 could function as an in cis acting inhibitor of antigen presentation. This may contribute to the immune evasion of cells latently infected by KSHV.
Zaldumbide
Arnaud
A
Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Ossevoort
Martine
M
Wiertz
Emmanuel J H J
EJ
Hoeben
Rob C
RC
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000378:metabolism*; D002460:Cell Line; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012514:Sarcoma, Kaposi / Q000276:immunology
D000956:Antigens, Viral; D009687:Nuclear Proteins; D010455:Peptides; C109540:latency-associated nuclear antigen