Abstract
Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8(+) cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and ultimately caused marked CD4(+) T cell depletion and AIDS-defining conditions. Transient treatment with an antibody to CD8 during acute HIV-1 infection caused rapid progression to AIDS, whereas untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection.
Copyright © 2014, American Association for the Advancement of Science.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acquired Immunodeficiency Syndrome / immunology
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Acquired Immunodeficiency Syndrome / transmission
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Acquired Immunodeficiency Syndrome / virology*
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Amino Acid Sequence
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD8 Antigens / immunology
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Disease Models, Animal*
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HIV-1 / genetics
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HIV-1 / physiology*
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Host-Pathogen Interactions / immunology*
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Human Immunodeficiency Virus Proteins / chemistry
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Human Immunodeficiency Virus Proteins / genetics
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Human Immunodeficiency Virus Proteins / metabolism
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Lymphocyte Depletion
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Macaca nemestrina / immunology
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Macaca nemestrina / virology*
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Molecular Sequence Data
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Protein Structure, Tertiary
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Viral Regulatory and Accessory Proteins / chemistry
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / metabolism
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Virus Replication
Substances
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CD8 Antigens
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Human Immunodeficiency Virus Proteins
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Viral Regulatory and Accessory Proteins
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vpu protein, Human immunodeficiency virus 1