High degree of sensitivity of the simian immunodeficiency virus (SIVmac) envelope glycoprotein subunit association to amino acid changes in the glycoprotein 41 ectodomain.
The infection of macaques by simian immunodeficiency virus (SIVmac) 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 SIVmac, result in similar phenotypes. In this study, we introduced amino acid changes into the SIVmac239 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 SIVmac239 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 SIVmac 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 SIVmacaque model.
Marcon
L
L
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Sodroski
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008715:Methionine; D008969:Molecular Sequence Data; D017354:Point Mutation; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D014364:Tryptophan; D014759:Viral Envelope Proteins
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins; C082614:SIV envelope protein gp41; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D014364:Tryptophan; D008715:Methionine