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Journal of Virology, January 2000, p. 254-263, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Induction of Antibodies in Guinea Pigs and Rhesus
Monkeys against the Human Immunodeficiency Virus Type 1 Envelope:
Neutralization of Nonpathogenic and Pathogenic Primary Isolate
Simian/Human Immunodeficiency Virus Strains
Hua-Xin
Liao,1,2,*
Bijan
Etemad-Moghadam,3
David C.
Montefiori,2,4
Ying
Sun,3
Joseph
Sodroski,3
Richard M.
Scearce,1,2
Robert W.
Doms,5
James R.
Thomasch,1,2
Suzanne
Robinson,6
Norman L.
Letvin,6 and
Barton F.
Haynes1,2,*
Departments of
Medicine1 and
Surgery4 and Center for AIDS
Research,2 Duke University Medical Center,
Durham, North Carolina 27710; Dana Farber Cancer
Institute3 and Beth Israel Deaconess
Medical Center,6 Harvard Medical School,
Boston, Massachusetts 02115; and Department of Pathology,
University of Pennsylvania, Philadelphia, Pennsylvania
191045
Received 30 March 1999/Accepted 10 September 1999
We have compared the abilities of human immunodeficiency virus type
1 (HIV-1) envelope V3 peptides and recombinant gp120 to induce
antibodies that neutralize simian/human immunodeficiency viruses
(SHIVs). SHIV-89.6 is a nonpathogenic SHIV that expresses the envelope
protein of primary HIV-1 isolate 89.6. SHIV-89.6P, clone KB9, is a
pathogenic SHIV variant derived from SHIV-89.6. Infection of rhesus
monkeys with these SHIVs rarely induces anti-V3 region antibodies. To
determine the availability of the gp120 V3 loop for neutralizing
antibody binding on SHIV-89.6 and KB9 virions, we have constructed
immunogenic C4-V3 peptides from these SHIVs and induced anti-V3
antibodies in guinea pigs and rhesus monkeys. We found that both
SHIV-89.6 and KB9 C4-V3 peptides induced antibodies that neutralized
SHIV-89.6 but that only SHIV-KB9 C4-V3 peptide induced antibodies that
neutralized SHIV-KB9. Immunoprecipitation assays demonstrated that
SHIV-KB9 C4-V3 peptide-induced antibodies had a greater ability to bind
SHIV-KB9 envelope proteins than did antibodies raised against SHIV-89.6
C4-V3 peptide. We have used a series of mutant HIV-1 envelope
constructs to map the gp120 determinants that affect neutralization by
anti-V3 antibodies. The residue change at position 305 of arginine (in
SHIV-89.6) to glutamic acid (in SHIV-KB9) played a central role in
determining the ability of peptide-induced anti-V3 antiserum to
neutralize primary isolate SHIVs. Moreover, residue changes in the
SHIV-89.6 V1/V2 loops also played roles in regulating the availability
of the V3 neutralizing epitope on SHIV-89.6 and -KB9. Thus, SHIV-89.6 and -KB9 V3 region peptides are capable of inducing neutralizing antibodies against these primary isolate SHIVs, although the pathogenic SHIV-KB9 is less easily neutralized than its nonpathogenic variant SHIV-89.6. In contrast to natural infection with SHIV-89.6, in which
few animals make anti-V3 antibodies, C4-V3 peptides frequently induced
anti-V3 antibodies that neutralized primary isolate SHIV strains.
*
Corresponding author. Mailing address: Duke University
Medical Center, Box 3258, Durham, NC 27710. Phone: (919) 684-5858. Fax:
(919) 684-5230. E-mail for Hua-Xin Liao:
hliao{at}acpub.duke.edu. E-mail for Barton F. Haynes:
hayne002{at}mc.duke.edu.
Journal of Virology, January 2000, p. 254-263, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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