Abstract
We have used coreceptor-targeted inhibitors to investigate which coreceptors are used by human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency viruses (SIV), and human immunodeficiency virus type 2 (HIV-2) to enter peripheral blood mononuclear cells (PBMC). The inhibitors are TAK-779, which is specific for CCR5 and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5 and CCR3, and AMD3100, which targets CXCR4. We found that for all the HIV-1 isolates and all but one of the HIV-2 isolates tested, the only relevant coreceptors were CCR5 and CXCR4. However, one HIV-2 isolate replicated in human PBMC even in the presence of TAK-779 and AMD3100, suggesting that it might use an undefined, alternative coreceptor that is expressed in the cells of some individuals. SIV(mac)239 and SIV(mac)251 (from macaques) were also able to use an alternative coreceptor to enter PBMC from some, but not all, human and macaque donors. The replication in human PBMC of SIV(rcm) (from a red-capped mangabey), a virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting that CCR2 is indeed the paramount coreceptor for this virus in primary cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amides / pharmacology
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Animals
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Anti-HIV Agents / pharmacology*
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Benzylamines
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CD4 Antigens / metabolism
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Cell Line
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Chemokine CCL5 / analogs & derivatives
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Chemokine CCL5 / pharmacology
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Cyclams
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HIV-1 / drug effects
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HIV-1 / pathogenicity
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HIV-1 / physiology*
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HIV-2 / drug effects
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HIV-2 / pathogenicity
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HIV-2 / physiology*
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Heterocyclic Compounds / pharmacology
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Humans
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Leukocytes, Mononuclear / virology
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Lymphocytes
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Macaca
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Quaternary Ammonium Compounds / pharmacology
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Receptors, CCR2
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Receptors, CCR3
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Receptors, CCR5 / metabolism
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Receptors, Chemokine / metabolism
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Receptors, HIV / antagonists & inhibitors
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Receptors, HIV / metabolism*
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Receptors, Virus / antagonists & inhibitors
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Receptors, Virus / metabolism*
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Simian Immunodeficiency Virus / drug effects
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Simian Immunodeficiency Virus / pathogenicity
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Simian Immunodeficiency Virus / physiology*
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Transfection
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Tumor Cells, Cultured
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Virus Replication / drug effects
Substances
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Amides
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Anti-HIV Agents
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Benzylamines
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CCR2 protein, human
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CCR3 protein, human
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CD4 Antigens
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Chemokine CCL5
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Cyclams
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Heterocyclic Compounds
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Quaternary Ammonium Compounds
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Receptors, CCR2
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Receptors, CCR3
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Receptors, CCR5
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Receptors, Chemokine
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Receptors, HIV
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Receptors, Virus
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aminooxypentane-RANTES
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TAK 779
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plerixafor