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Journal of Virology, February 1999, p. 976-984, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Changes in Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Responsible for the Pathogenicity of a
Multiply Passaged Simian-Human Immunodeficiency Virus
(SHIV-HXBc2)
Mark
Cayabyab,1,2
Gunilla B.
Karlsson,1
Bijan A.
Etemad-Moghadam,1
Wolfgang
Hofmann,1
Tavis
Steenbeke,3
Matilda
Halloran,3
John W.
Fanton,4
Michael K.
Axthelm,4
Norman L.
Letvin,3 and
Joseph G.
Sodroski1,2,*
Department of Cancer Immunology/AIDS,
Dana-Farber Cancer Institute, Department of
Pathology1 and
Division of Viral
Pathogenesis, Beth Israel Deaconess Medical
Center,3 Harvard Medical School, and
Department of Immunology and Infectious Diseases, Harvard
School of Public Health,2 Boston, Massachusetts
02115, and
Oregon Regional Primate Research Center,
Beaverton, Oregon 97006-34994
Received 14 July 1998/Accepted 14 October 1998
In vivo passage of a poorly replicating, nonpathogenic simian-human
immunodeficiency virus (SHIV-HXBc2) generated an efficiently replicating virus, KU-1, that caused rapid CD4+
T-lymphocyte depletion and AIDS-like illness in monkeys (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L.-J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol.
70:3189-3197, 1996). The env gene of the KU-1 virus was
used to create a molecularly cloned virus, SHIV-HXBc2P 3.2, that
differed from a nonpathogenic SHIV-HXBc2 virus in only 12 envelope
glycoprotein residues. SHIV-HXBc2P 3.2 replicated efficiently and
caused rapid and persistent CD4+ T-lymphocyte depletion in
inoculated rhesus macaques. Compared with the envelope glycoproteins of
the parental SHIV-HXBc2, the SHIV-HXBc2P 3.2 envelope glycoproteins
supported more efficient infection of rhesus monkey peripheral blood
mononuclear cells. Both the parental SHIV-HXBc2 and the pathogenic
SHIV-HXBc2P 3.2 used CXCR4 but none of the other seven transmembrane
segment receptors tested as a second receptor. Compared with the
parental virus, viruses with the SHIV-HXBc2P 3.2 envelope glycoproteins
were more resistant to neutralization by soluble CD4 and antibodies.
Thus, changes in the envelope glycoproteins account for the ability of
the passaged virus to deplete CD4+ T lymphocytes rapidly
and specify increased replicative capacity and resistance to neutralization.
*
Corresponding author. Mailing address: Department of
Cancer Immunology/AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02115. Phone: (617) 632-3371. Fax:
(617) 632-4338. E-mail:
joseph_sodroski{at}dfci.harvard.edu.
Journal of Virology, February 1999, p. 976-984, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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