Inhibition of intracellular transport of B cell antigen receptor complexesby Kaposi's sarcoma-associated herpesvirus K1

The B cell antigen receptor (BCR) is a large complex that consists of a dis ulfide-linked tetramer of two transmembrane heavy (mu) chains and two light (lambda or kappa) chains in association with a heterodimer of Ig alpha and Ig beta, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a transfor ming protein called K1, which has structural and functional similarity to I g alpha and Ig beta. We demonstrate that K1 downregulates the expression of BCR complexes on the surface. The NH2-terminal region of K1 specifically i nteracts with the mu 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 alpha and Ig bet a in its ability to induct signaling and to interact with mu chains of the BCR. However, unlike Ig alpha and Ig beta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu chains to b lock the intracellular transport of BCR complexes to the cell surface, Thes e results demonstrate a unique feature of the K1 transforming protein, whic h may confer virus-infected cells with a long-term survival advantage.