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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antiviral Agents / immunology
-
CD4-Positive T-Lymphocytes / immunology*
-
CD4-Positive T-Lymphocytes / virology
-
Chimera / immunology
-
Giant Cells / virology
-
HIV-1 / genetics
-
HIV-1 / immunology*
-
HIV-1 / pathogenicity
-
Humans
-
Lymph Nodes / virology
-
Lymphocyte Count
-
Lymphocyte Depletion*
-
Macaca mulatta
-
Neutralization Tests
-
Protein Structure, Tertiary
-
Simian Acquired Immunodeficiency Syndrome / genetics
-
Simian Acquired Immunodeficiency Syndrome / immunology*
-
Simian Acquired Immunodeficiency Syndrome / virology
-
Simian Immunodeficiency Virus / genetics
-
Simian Immunodeficiency Virus / immunology
-
Simian Immunodeficiency Virus / pathogenicity
-
Viral Envelope Proteins / chemistry
-
Viral Envelope Proteins / genetics
-
Viral Envelope Proteins / physiology*
-
Virus Replication / genetics
-
Virus Replication / immunology
Substances
-
Antiviral Agents
-
Viral Envelope Proteins