We have extended our mechanistic studies of virus-receptor interactions, with focus on two specific enveloped viruses: 1) Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8). We have generated a battery of monoclonal antibodies (Mabs) against glycoprotein H (gH), elicited by immunizing mice with a soluble construct representing the entire extracellular portion of gH. One of these mAbs potently inhibits KSHV entry (as assessed using a KSHV recombinant encoding the EGFP reporter gene). The effect is at a post-binding step, since the antibody had no effect on virion biinding (in contrast with heparan, which effectively blocked virion binding). Studies with truncated gH constructs and a panel of gH-based peptides have allowed us to generate an epitope map for the 13 ant-gH mAbs that we generated (manuscript in preparation). 2) Hepatitis C virus (HCV). Using specialized mammalian producer cell line carrying a West Nile virus replicon, we have devised a novel system to generate infectious HCV particles (genotype 1a) in which all viral-encoded components (proteins and RNA) are derived from HCV. We have shown that the system can generate infectious particles carrying full-length HCV genomes that replicate in HCV-permissive target cells as well as human liver slices. Evidence suggests that the ability of the WNV-replicon cell line to secrete infectious HCV particles is due not to ongoing function of the WNV replicon, but rather to intracellular changes (presumably including membrane rearrangements) induced by the replicon (Triyatni et al., manuscript submitted).
| Triyatni, Miriam; Berger, Edward A; Saunier, Bertrand (2016) Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway. World J Hepatol 8:796-814 |
| 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 |
