SPECIFIC TARGETING TO CD4(-IMMUNODEFICIENCY-VIRUS ENVELOPE PROTEINS()CELLS OF RECOMBINANT VESICULAR STOMATITIS VIRUSES ENCODING HUMAN)

We generated replication-competent, recombinant vesicular stomatitis v iruses (VSVs) expressing the human immunodeficiency virus (HIV) envelo pe protein or an HIV-VSV chimeric envelope protein in which the cytopl asmic domain of the HIV envelope protein was replaced with that from t he VSV glycoprotein (G). These recombinants mere generated with HIV ty pe 1 (HIV-1) envelopes from both laboratory and primary isolates of HI V-1. The replication-competent recombinant viruses were stable and exp ressed the foreign proteins at high levels from extra transcription un its in VSV. The foreign proteins were processed appropriately and tran sported to the cell surface, The incorporation of HIV gp120 into VSV p articles was demonstrated biochemically only for the construct express ing the chimeric envelopes containing the VSV G cytoplasmic domain, Th e incorporation of the chimeric HIV envelope protein into the membrane of the recombinant VSV was also demonstrated by electron microscopy w ith gold-conjugated antibodies, To determine whether specific infectio n of CD3-positive cells could be demonstrated far these recombinants, we neutralized VSV infectivity due to VSV glycoprotein with anti-VSV s erum, The neutralized recombinants expressing the chimeric envelope we re able to infect only HeLa cells expressing CD4, and this CD4-specifi c infectivity was neutralized with anti-HIV serum, This assay also det ected a 100-fold-lower titer of CD4-specific infectivity for the VSV r ecombinant expressing the wild-type HIV envelope, Our results illustra te that it is possible to express functional HIV envelopes from the VS V genome and target the recombinant virus to an alternative receptor, The recombinants may also prove useful as HIV vaccines.