Previous Article | Next Article ![]()
Journal of Virology, July 1999, p. 5294-5300, Vol. 73, No. 7
Aaron Diamond AIDS Research Center, The
Rockefeller University, New York, New York
10016,1 and Department of Medical
Pathology, University of California, Davis, California
956162
Received 27 October 1998/Accepted 16 March 1999
We previously reported on the in vivo adaptation of an infectious
molecular simian/human immunodeficiency virus (SHIV) clone, SHIVSF33, into a pathogenic biologic viral variant,
designated SHIVSF33A. In the present study, we show that
SHIVSF33A is resistant to neutralization by human
immunodeficiency virus (HIV) and SHIV antisera. Multiple amino acid
substitutions accumulated over time throughout the env gene
of SHIVSF33A; some of them coincided with the acquisition
of the neutralization resistance of the virus. Of interest are changes
that resulted in the removal, repositioning, and addition of potential
glycosylation sites within the V1, V2, and V3 regions of envelope
gp120. To determine whether potential glycosylation changes within
these principal neutralization domains of HIV type 1 formed the basis
for the resistance to serum neutralization of SHIVSF33A,
mutant viruses were generated on the backbone of parental
SHIVSF33 and tested for their neutralization sensitivity. The mutations generated did not alter the in vitro replication kinetics
or cytopathicity of the mutant viruses in T-cell lines. However, the
removal of a potential glycosylation site in the V1 domain or the
creation of such a site in the V3 domain did allow the virus to escape
serum neutralization antibodies that recognized parental
SHIVSF33. The combination of the V1 and V3 mutations
conferred an additive effect on neutralization resistance over that of
the single mutations. Taken together, these data suggest that (i) SHIV
variants with changes in the Env SU can be selected in vivo primarily
by virtue of their ability to escape neutralizing antibody recognition
and (ii) carbohydrates play an important role in conferring
neutralization escape, possibly by altering the structure of envelope
gp120 or by shielding principal neutralization sites.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Selection for Neutralization Resistance of the
Simian/Human Immunodeficiency Virus SHIVSF33A Variant In
Vivo by Virtue of Sequence Changes in the Extracellular Envelope
Glycoprotein That Modify N-Linked Glycosylation
*
Corresponding author. Mailing address: Aaron Diamond
AIDS Research Center, 455 First Ave., New York, NY 10016. Phone: (212) 448-5080. Fax: (212) 448-5159. E-mail: cmayer{at}adarc.org.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|