Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4

Elena Ryzhova, J. Charles Whitbeck, Gabriela Canziani, Susan V. Westmoreland, Gary H. Cohen, Roselyn J. Eisenberg, Andrew Lackner, Francisco González-Scarano

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Aspartate 368 on human immunodeficiency virus type 1 (HIV-1) gp120 forms multiple contacts with CD4; in mutagenesis studies, its replacement by asparagine and corresponding changes in simian immunodeficiency virus SIVmac (D385N) reduced binding with CD4. Nevertheless, simian immunodeficiency virus envelopes with D385N were prevalent in several studies. Extending these observations, we also found D385N to be dominant among env clones from two rhesus macaques that progressed rapidly to simian AIDS. These envelopes showed a CD4-independent phenotype as well as reduced affinity to CD4. Moreover, an adjacent change, G383R, which was frequently coselected with D385N, further decreased binding. An optical biosensor study demonstrated that the SIVmac239 gp120 bound to CD4 with kinetics similar to those of HIV-1. However, the gp120s with D385N and G383R showed a 40-fold reduction in affinity, with a drastic increase in dissociation rate, indicating an inherently unstable complex. This finding showed that rapid progression to simian AIDS may be accompanied by the selection of CD4-independent gp120 variants with impaired CD4 binding ability.

Original languageEnglish (US)
Pages (from-to)7903-7909
Number of pages7
JournalJournal of Virology
Volume76
Issue number15
DOIs
StatePublished - 2002
Externally publishedYes

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Simian Acquired Immunodeficiency Syndrome
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Human immunodeficiency virus 1
HIV-1
biosensors
Asparagine
binding capacity
Biosensing Techniques
asparagine
aspartic acid
Macaca mulatta
Aspartic Acid
mutagenesis
Mutagenesis
Clone Cells
clones
Phenotype
phenotype
kinetics

ASJC Scopus subject areas

  • Immunology

Cite this

Ryzhova, E., Whitbeck, J. C., Canziani, G., Westmoreland, S. V., Cohen, G. H., Eisenberg, R. J., ... González-Scarano, F. (2002). Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. Journal of Virology, 76(15), 7903-7909. https://doi.org/10.1128/JVI.76.15.7903-7909.2002

Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. / Ryzhova, Elena; Whitbeck, J. Charles; Canziani, Gabriela; Westmoreland, Susan V.; Cohen, Gary H.; Eisenberg, Roselyn J.; Lackner, Andrew; González-Scarano, Francisco.

In: Journal of Virology, Vol. 76, No. 15, 2002, p. 7903-7909.

Research output: Contribution to journalArticle

Ryzhova, E, Whitbeck, JC, Canziani, G, Westmoreland, SV, Cohen, GH, Eisenberg, RJ, Lackner, A & González-Scarano, F 2002, 'Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4', Journal of Virology, vol. 76, no. 15, pp. 7903-7909. https://doi.org/10.1128/JVI.76.15.7903-7909.2002
Ryzhova, Elena ; Whitbeck, J. Charles ; Canziani, Gabriela ; Westmoreland, Susan V. ; Cohen, Gary H. ; Eisenberg, Roselyn J. ; Lackner, Andrew ; González-Scarano, Francisco. / Rapid progression to simian AIDS can be accompanied by selection of CD4-independent gp120 variants with impaired ability to bind CD4. In: Journal of Virology. 2002 ; Vol. 76, No. 15. pp. 7903-7909.
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