Enveloped Virus Glycoprotein/receptor Interactions

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

In FY2015, we extended our previous findings that the KSHV virion K8.1A glycoprotein, previously proposed to be dispensable for KSHV infection, is essential for infection of B cells. We demonstrated this with both the MC116 B cell line and with human tonsillar B cells, suggesting that K8.1A is a critical determinant of KSHV B cell tropism. We have made the surprising observation that the K8.1A involvement in B cell infection is independent of the only reported activity of this viral glycoprotein, namely binding to heparan sulfate proteoglycans. By analogy with genetic positional homologs of K8.1 in other gammaherpesviruses, these findings suggest the possible existence of an additional (B cell-specific) cellular receptor, perhaps a surface protein. Companion studies have focused on the relationship between the KSHV producer cell line and the cellular tropism of the corresponding virions. As a component of this work we generated constitutively infected variants of MC116 B cells and TIME microvascular endothelial cells in which lytic phase is induced by doxycycline. Preliminary data point to profound differences in the tropism of KSHV virions dependent on the producer cell type. In a collaborative effort with Dr. Robert Yarchoan, we have begun to examine antibodies in sera of patients with different KSHV-associated pathologies, for neutralizing activities against different target cell types and for reactivities with specific KSHV glycoproteins.