title: Mechanisms of HIV-1 neurotropism.
abstract: Human immunodeficiency virus type 1 (HIV) infects macrophages and microglia in the CNS and frequently causes neurocognitive impairment. Although antiviral therapy generally reduces the viral load in the CNS and improves HIV-associated neurological dysfunction, most current antiviral drugs have poor CNS penetrance and cannot completely suppress viral replication. Furthermore, drug-resistance mutations can evolve independently in the CNS. Thus, a long-lived viral reservoir persists in macrophages and microglia in the brain despite antiviral therapy. This review discusses mechanisms underlying the neurotropism of HIV, focusing on the role of the HIV envelope glycoproteins and their interactions with CD4 and the chemokine receptors CCR5 and CXCR4. We review data from studies of neurotropic HIV derived from the brains of patients with HIV-associated neurocognitive impairment as well as studies of nonhuman primate models. Understanding mechanisms that underlie HIV neurotropism and neurovirulence is critical for development of therapeutics to inhibit CNS infection and preventing neurological injury in HIV-infected individuals.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dunfee
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Thomas
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Jianbin
authors.initials: J
authors.lastname: Wang
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000821:virology; D001921:Brain / Q000821:virology*; D015704:CD4 Antigens / Q000502:physiology; D002465:Cell Movement; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology; D009000:Monocytes / Q000502:physiology; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D017452:Receptors, IgG / Q000032:analysis; D018523:Tropism / Q000502:physiology*; D014774:Virulence
chemical_list: D015704:CD4 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017452:Receptors, IgG