Expression of human immunodeficiency virus type 1 Gag protein precursor and envelope proteins from a vesicular stomatitis virus recombinant: High-level production of virus-like particles containing HIV envelope

Recombinant vesicular stomatitis viruses have been developed as high-level expression vectors which serve as effective vaccine vectors in animals (Rob erts et al., 1998. J. Virol. 72, 4704-4711; Roberts er at, 1999, J. Virol. 73, 3723-3732). Here we show that two genes can be expressed simultaneously from a single, live-attenuated VSV recombinant The genes used encode the p r55(gag) protein precursor of HIV-1 (1.7-kb gene) and an HIV-1 envelope (En v) protein (2.4 kb gene). Our results show that VSV can accommodate up to a 40% increase in genome sire with only a threefold reduction in virus titer . Recombinants expressing the Pr55(gag) protein precursor with or without E nv protein produced abundant HIV virus-like particles (VLPs) in addition to bullet-shaped VSV particles. HIV Env protein expressed from a VSV recombin ant also expressing Gag was specifically incorporated into the HIV VLPs but not into the VSV particles. In contrast, VSV G protein was found in both V SV particles and in HIV VLPs. Such VSV/HIV recombinants producing HIV VLPs with Env protein could be an effective source of HIV-like particles inducin g both cellular and antibody-mediated immunity to HIV-1. (C) 2000 Academic Press.