In FY2014, we extended our findings on KSHV infection of MC116 cells with the following demonstrations: 1. MC116 cells are capable of productive KSHV replication. Beyond susceptibility to KSHV entry and production of viral gene products associated with latency, activation of infected MC116 cells leads to expression of lytic genes and to production of infectious KSHV virions. 2. A KSHV glycoprotein that is critical for B cell tropism. Like all herpesviruses, KSHV encodes several virion-associated glycoproteins that contribute to entry/tropism. We found that one of these glycoproteins is critical for KSHV entry into B cells, but not into other target cell types (e.g. 293 cells, Vero cells). This conclusion was based on the selective inhibitory activity of mAbs against this glycoprotein for MC116 infection but not infection of other target cells, as well as the selective loss of B cell infection in a mutant virus with a deletion of this glycoprotein. 3. This KSHV glycoprotein is also involved in KSHV infection of primary B cells. The anti-glycoprotein mAb was found to inhibit infection of tonsillar B cells (approximately 50%). This finding, along with other data, suggest that MC116 cells display a critical tropism parameter characteristic of primary B cells. 4. Surface proteoglycans play a critical role for KSHV infection of MC116 cells and tonsillar B cells.
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| Berger, Edward A (2015) Finding Fusin/CXCR4, the First ""2nd Receptor"" for HIV Entry. Front Immunol 6:283 |
| Dollery, Stephen J; Santiago-Crespo, Rey J; Kardava, Lela et al. (2014) Efficient infection of a human B cell line with cell-free Kaposi's sarcoma-associated herpesvirus. J Virol 88:1748-57 |
| Triyatni, Miriam; Berger, Edward A; Saunier, Bertrand (2011) A new model to produce infectious hepatitis C virus without the replication requirement. PLoS Pathog 7:e1001333 |
