Herpes Viruses Sabotage Histocompatibility Complex

The study was published in the January 2003 issue of Immunity.

Researchers from Washington University School of Medicine (St. Louis, MO, USA) found that the viral mK3 protein acted as a pseudo-chaperone molecule during the assembly of MHC class I molecules by the TAP/tapasin complex.

Tapasin is a transmembrane glycoprotein located in the endoplasmic reticulum that plays an important role in the assembly and peptide binding process of the MHC class I molecule. Tapasin is a subunit of the protein complex consisting of the transporter associated with antigen processing (TAP), MHC class I, and the chaperone molecule calreticulin. Tapasin binds to TAP1 and to beta-2 microglobulin (after beta-2 m has bound the MHC I alpha chain), thus acting as a bridge between the MHC I molecule and the TAP1/2 complex.

The viral mK3 protein joined the TAP/tapasin complex as a pseudo-chaperone molecule and labeled the MHC I molecule with ubiquitin, which marked it for destruction by cellular proteasomes. The destruction of the MHC molecule prevented expression of viral antigens on the cell surface and prevented the immune system from recognizing the herpes virus.

"These findings not only provide a better understanding of viral infections,” explained senior author Dr. Ted H. Hansen, professor of genetics at Washington University School of Medicine. "They also offer novel insights into basic cellular processes in the immune system.”



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Washington University School of Medicine