In cis inhibition of antigen processing by the latency-associated nuclear antigen I of Kaposi sarcoma herpes virus.

Abstract

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.

• Authors: Arnaud Zaldumbide, Martine Ossevoort, Emmanuel J H J Wiertz, Rob C Hoeben
• Journal: Molecular immunology (Mol Immunol) Vol. 44 Issue 6 Pg. 1352-60 (Feb 2007) ISSN: 0161-5890 [Print] England
• PMID: 16828498 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antigens, Viral
• Nuclear Proteins
• Peptides
• latency-associated nuclear antigen

Topics

• Amino Acid Sequence
• Antigen Presentation (immunology)
• Antigens, Viral (metabolism)
• Cell Line
• Herpesvirus 8, Human (immunology)
• Humans
• Immunosuppression Therapy
• Molecular Sequence Data
• Nuclear Proteins (antagonists & inhibitors, metabolism)
• Peptides (antagonists & inhibitors, immunology)
• Protein Structure, Tertiary (physiology)
• Sarcoma, Kaposi (immunology)