Glycoprotein K8.1A of Kaposi's Sarcoma-Associated Herpesvirus Is a Critical B Cell Tropism Determinant Independent of Its Heparan Sulfate Binding Activity

Abstract

Elucidating the molecular mechanisms by which KSHV infects B lymphocytes is critical for understanding how the virus establishes lifelong persistence in infected people, in whom it can cause life-threatening B cell lymphoproliferative disease. Here, we show that K8.1A, a KSHV-encoded glycoprotein on the surfaces of the virus particles, is critical for infection of B cells. This finding stands in marked contrast to previous studies with non-B lymphoid cell types, for which K8.1A is known to be dispensable. We also show that the required function of K8.1A in B cell infection does not involve its binding to cell surface heparan sulfate, the only known biochemical activity of the glycoprotein. The discovery of this critical role of K8.1A in KSHV B cell tropism opens promising new avenues to unravel the complex mechanisms underlying infection and disease caused by this viral human pathogen.