A novel monoclonal antibody specific to the C-terminal tail of the gp41 envelope transmembrane protein of human immunodeficiency virus type 1 that preferentially neutralizes virus after it has attached to the target cell and inhibits the production of infectious progeny

AbstractSAR1 is a new IgG2a murine monoclonal antibody derived by immunization with a plant virus expressing the sequence GERDRDR from the C-terminal tail of the gp41 transmembrane glycoprotein of human immunodeficiency virus type 1 (HIV-1). SAR1 binds to peptides and proteins carrying the GERDRDR sequence, to some but not all preparations of purified virus, and to cells infected with all viruses tested. In a standard neutralization assay, SAR1 failed to neutralize, or neutralized poorly, a number of T cell line-adapted viruses. However, it was more effective at postattachment neutralization. This was measured by two assays, the inhibition of the syncytium production by input virus, and the inhibition of the production of infectious progeny virus. In general SAR1 was more effective at neutralizing progeny virus than inoculum virus. Fifty percent inhibition of progeny virus production by different HIV-1 strains was obtained with 2–26 μg/ml of SAR1. The SAR1 neutralizing epitope was mapped specifically to the gp41 C-terminal tail. SAR1 is an unusual, if not unique, antibody whose activity supports the view that part of the gp41 C-terminal tail is exposed on the outside of the virion