NIH Research Festival
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NIAID
VIROL-1
Infection of B cells by Kaposi’s sarcoma-associated herpesvirus (KSHV) is of critical importance. Latently infected B cells are a major KSHV reservoir and KSHV is causatively linked to two B cell lymphoproliferative disorders; multicentric Castleman’s disease and primary effusion lymphoma. In addition, virus activation from tonsillar B cells is thought to result in salivary shedding and virus transmission. Virus entry of KSHV into B cells remains poorly understood and infection of B cell lines and primary B cells with cell free virus is notoriously difficult. Here we show that numerous B cell lines, previously thought to be non-permissive, can be infected with antibody pre-treated KSHV. Using anti-K8.1A antibody treated KSHV.219, we found that RAJI cells permit the highest levels of detectable infection in the cell lines tested (30%-EGFP+). Newly infected cells expressed latency associated nuclear antigen (LANA) in nuclear foci. Following selection and induction, KSHV.219 infected RAJI cells were able to enter lytic replication, synthesize late proteins and generate infectious virus, thus verifying productive infection. Further characterization of infection revealed that the antibody enhanced infection is dependent upon antibody binding to the FC gamma II receptor/CD32 and virus simultaneously. We previously presented that the MC116 B cell line is up to 20 percent susceptible to KSHV infection, and that KSHV glycoprotein K8.1A is a crucial requirement for infection of MC116 B cells, but not non-B cells. Directly comparing the two systems, we find that the same concentrations of anti-K8.1A antibodies that inhibit infection of MC116 cells enhance entry into RAJI cells in a dose dependent manner. This indicates the existence of two potential distinct mechanisms/pathways for infection of B cells. These findings may have implications for pathogenesis, especially given the abundance of anti-K8.1 antibodies produced during typical infection.
Scientific Focus Area: Virology
This page was last updated on Friday, March 26, 2021