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Journal of Virology, October 1999, p. 8873-8879, Vol. 73, No. 10
Department of Cancer Immunology and AIDS,
Received 29 March 1999/Accepted 7 July 1999
In vivo passage of a simian-human immunodeficiency virus
(SHIV-89.6) generated a virus, SHIV-89.6P, that exhibited increased resistance to some neutralizing antibodies (G. B. Karlsson et al.,
J. Exp. Med. 188:1159-1171, 1998). Here we examine the range of human
immunodeficiency virus type 1 (HIV-1) neutralizing antibodies to which
the passaged virus became resistant and identify envelope glycoprotein
determinants of antibody resistance. Compared with the envelope
glycoproteins derived from the parental SHIV-89.6, the envelope
glycoproteins of the passaged virus were resistant to antibodies
directed against the gp120 V3 variable loop and the CD4 binding site.
By contrast, both viral envelope glycoproteins were equally sensitive
to neutralization by two antibodies, 2G12 and 2F5, that recognize
poorly immunogenic structures on gp120 and gp41, respectively. Changes
in the V2 and V3 variable loops of gp120 were necessary and sufficient
for full resistance to the IgG1b12 antibody, which is directed against
the CD4 binding site. Changes in the V3 loop specified complete
resistance to a V3 loop-directed antibody, while changes in the V1/V2
loops conferred partial resistance to this antibody. The epitopes of the neutralizing antibodies were not disrupted by the
resistance-associated changes. These results indicate that in vivo
selection occurs for HIV-1 envelope glycoproteins with variable loop
conformations that restrict the access of antibodies to immunogenic
neutralization epitopes.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Determinants of Neutralization Resistance in the
Envelope Glycoproteins of a Simian-Human Immunodeficiency Virus
Passaged In Vivo
*
Corresponding author. Mailing address: Division of
Human Retrovirology, Dana-Farber Cancer Institute, 44 Binney St., JFB
824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338. E-mail: Joseph_Sodroski{at}dfci.harvard.edu.
Journal of Virology, October 1999, p. 8873-8879, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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