TRUNCATIONS OF THE SIMIAN IMMUNODEFICIENCY VIRUS TRANSMEMBRANE PROTEIN CONFER EXPANDED VIRUS HOST-RANGE BY REMOVING A BLOCK TO VIRUS ENTRY INTO CELLS

We have investigated how truncation of the cytoplasmic domain of the t ransmembrane (TM) glycoprotein of simian immunodeficiency virus (SIV) modulates the host range of this virus. Termination codons were introd uced into the env gene of SIV(mac)239 which resulted in the truncation of the transmembrane protein from a wild-type 354 amino acids (TM354) to 207 (TM207) and 193 (TM193) amino acids. Expression of the wild-ty pe and mutant env genes from a simian virus 40-based vector resulted i n normal biosynthesis and processing of the glycoproteins to gp130 and gp41 or the truncated TM proteins (gp28 and gp27). When expressed on the surface of COS-1 cells, all three glycoproteins mediated fusion of both CEMX174 and HUT78 cells. Virions containing the wild-type and mu tant glycoproteins were capable of efficient replication in macaque pe ripheral blood lymphocytes and CEMX174 cells; in contrast, only virion s that contained TM207 were capable of rapid infection of HUT78 cells. Both truncated glycoproteins were capable of efficiently mediating in fection of both CEMX174 and HUT78 cells by an env-deficient human immu nodeficiency virus. The wild-type SIV glycoprotein, however, was unabl e to mediate human immunodeficiency virus infection of HUT78 cells whe n assayed with this system. An analysis of the protein composition of SIV released from infected CEMX174 cells showed that the mutant virion s contained significantly higher levels of glycoprotein compared with the wild type. These results demonstrate that truncation of the SIV cy toplasmic domain removes a block at the level of glycoprotein-mediated virus entry into HUT78 cells and points to a role for glycoprotein de nsity in determining virus tropism.