Original Article

Inhibition of Intracellular Transport of B Cell Antigen Receptor Complexes by Kaposi's Sarcoma–associated Herpesvirus K1

Correspondence to: Jae U. Jung, Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, 1 Pine Hill Dr., Southborough, MA 01772. Tel:508-624-8083 Fax:508-786-1416 E-mail:jae_jung{at}hms.harvard.edu.

The B cell antigen receptor (BCR) is a large complex that consists of a disulfide-linked tetramer of two transmembrane heavy (µ) chains and two light ( or ) chains in association with a heterodimer of Ig and Igß. Kaposi's sarcoma–associated herpesvirus (KSHV) encodes a transforming protein called K1, which has structural and functional similarity to Ig and Igß. We demonstrate that K1 downregulates the expression of BCR complexes on the surface. The NH₂-terminal region of K1 specifically interacts with the µ chains of BCR complexes, and this interaction retains BCR complexes in the endoplasmic reticulum, preventing their intracellular transport to the cell surface. Thus, KSHV K1 resembles Ig and Igß in its ability to induce signaling and to interact with µ chains of the BCR. However, unlike Ig and Igß, which interact with µ chains to direct BCR complexes to the cell surface, K1 interacts with µ chains to block the intracellular transport of BCR complexes to the cell surface. These results demonstrate a unique feature of the K1 transforming protein, which may confer virus-infected cells with a long-term survival advantage.

Key Words: Kaposi's sarcoma–associated herpesvirus, K1, B cell antigen receptor, downregulation, intracellular transport

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