High Degree of Sensitivity of the Simian Immunodeficiency Virus (SIV mac ) Envelope Glycoprotein Subunit Association to Amino Acid Changes in the Glycoprotein 41 Ectodomain

The infection of macaques by simian immunodeficiency virus (SIV_mac) represents an attractive model to study the pathogenic determinants of primate and human immunodeficiency viruses. The utility of this model would be enhanced if genetic changes in human immunodeficiency virus (HIV-1) associated with interesting in vitro properties would, when introduced into SIV_mac, result in similar phenotypes. In this study, we introduced amino acid changes into the SIV_mac239 envelope glycoproteins that, in the context of the HIV-1 envelope glycoproteins, disproportionately attenuated in vitro cytopathic effects compared with the viral replication rate. Amino acid changes in the SIV_mac239 gp41 ectodomain altered the noncovalent association of the gp120 and gp41 glycoproteins significantly more than did analogous changes in the HIV-1 envelope glycoproteins. Decreases in the affinity of the gp120-gp41 interaction were observed and were associated with a dramatic attenuation of virus replication not seen in the HIV-1 studies. The increased sensitivity of the SIV_mac gp120-gp41 interaction to amino acid changes presents an obstacle to the direct extension of results obtained with the HIV-1 envelope glycoproteins to the SIV-macaque model.