Replication-competent rhabdoviruses with human immunodeficiency virus type1 coats and green fluorescent protein: Entry by a pH-independent pathway

We describe a replication-competent, recombinant vesicular stomatitis virus (VSV) in which the gene encoding the single transmembrane glycoprotein (G) was deleted and replaced by an env-G hybrid gene encoding the extracellula r and transmembrane domains of a human immunodeficiency virus type 1 (HIV-1 ) envelope protein fused to the cytoplasmic domain of VSV G. An additional gene encoding a green fluorescent protein was added to permit rapid detecti on of infection. This novel surrogate virus infected and propagated on cell s expressing the HIV receptor CD4 and coreceptor CXCR4. Infection was block ed by SDF-1, the ligand for CXCR4, by antibody to CD4 and by HN-neutralizin g antibody. This virus, unlike VSV, entered cells by a pH-independent pathw ay and thus supports a pa-independent pathway of HIV entry. Additional reco mbinants carrying hybrid env-G genes derived from R5 or X4R5 HIV strains al so showed the coreceptor specificities of the HIV strains from which they w ere derived. These surrogate viruses provide a simple and rapid assay for H IV-neutralizing antibodies as well as a rapid screen for molecules that wou ld interfere with any stage of HIV binding or entry. The viruses might also be useful as HIV vaccines. Our results suggest wide applications of other surrogate viruses based on VSV.