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PMID: 9743534 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.

The Journal of experimental medicine ·Vol. 188 ·No. 6 ·1998-09-21 ·Pages 1159-71

Karlsson GB, Halloran M, Schenten D, Lee J, Racz P, Tenner-Racz K, Manola J, Gelman R, Etemad-Moghadam B, Desjardins E, Wyatt R, Gerard NP, Marcon L, Margolin D, Fanton J, Axthelm MK, Letvin NL, Sodroski J

Abstract

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

MeSH Terms
Animals Antiviral Agents/immunology CD4-Positive T-Lymphocytes/immunology,virology Chimera/immunology Giant Cells/virology HIV-1/genetics,immunology,pathogenicity Humans Lymph Nodes/virology Lymphocyte Count Lymphocyte Depletion Macaca mulatta Neutralization Tests Protein Structure, Tertiary Simian Acquired Immunodeficiency Syndrome/genetics,immunology,virology Simian Immunodeficiency Virus/genetics,immunology,pathogenicity Viral Envelope Proteins/chemistry,genetics,physiology Virus Replication/genetics,immunology
Chemicals
Antiviral Agents Viral Envelope Proteins
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Karlsson G B
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Halloran M
Schenten D
Lee J
Racz P
Tenner-Racz K
Manola J
Gelman R
Etemad-Moghadam B
Desjardins E
Wyatt R
Gerard N P
Marcon L
Margolin D
Fanton J
Axthelm M K
Letvin N L
Sodroski J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.6.1159
Published
1998-09-21
Pages
1159-71
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212530
Subset
IM
Grants
NCI NIH HHS · CA-50139 · United States
NIAID NIH HHS · AI-20729 · United States
NCI NIH HHS · CA-06516 · United States
External Links
PubMed source DOI: 10.1084/jem.188.6.1159 PMC Full Text View journal details
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