Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1.
The B cell antigen receptor (BCR) is a large complex that consists of a disulfide-linked tetramer of two transmembrane heavy (mu) chains and two light (lambda or kappa) chains in association with a heterodimer of Igalpha and Igbeta. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a transforming protein called K1, which has structural and functional similarity to Igalpha and Igbeta. We demonstrate that K1 downregulates the expression of BCR complexes on the surface. The NH(2)-terminal region of K1 specifically interacts 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 Igalpha and Igbeta in its ability to induce signaling and to interact with mu chains of the BCR. However, unlike Igalpha and Igbeta, which interact with mu chains to direct BCR complexes to the cell surface, K1 interacts with mu 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.
Lee
B S
BS
Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Alvarez
X
X
Ishido
S
S
Lackner
A A
AA
Jung
J U
JU
D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000502:physiology; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry / Q000502:physiology; D007148:Immunoglobulin mu-Chains / Q000737:chemistry / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D016366:Open Reading Frames; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C111600:K1 protein, Human herpesvirus 8