title: HIV-1 envelope-receptor interactions required for macrophage infection and implications for current HIV-1 cure strategies.
abstract: Myeloid cells residing in the CNS and lymphoid tissues are targets for productive HIV-1 replication, and their infection contributes to the pathological manifestations of HIV-1 infection. The Envs can adopt altered configurations to overcome entry restrictions in macrophages via a more efficient and/or altered mechanism of engagement with cellular receptors. This review highlights evidence supporting an important role for macrophages in HIV-1 pathogenesis and persistence, which need to be considered for strategies aimed at achieving a functional or sterilizing cure. We also highlight that the molecular mechanisms underlying HIV-1 tropism for macrophages are complex, involving enhanced and/or altered interactions with CD4, CCR5, and/or CXCR4, and that the nature of these interactions may depend on the anatomical location of the virus.
authors.affiliation: 1.GPO Box 2284, Melbourne 3001, Victoria, Australia. gorry@burnet.edu.au or University of Pennsylvania, 522 Johnson Pavilion, 36th and Hamilton Walk, Philadelphia, PA 19104-6060, USA. E-mail: collmanr@mail.med.upenn.edu.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Nicholas
authors.initials: N
authors.lastname: Francella
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Collman
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000378:metabolism; D018450:Disease Progression; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D056189:Viral Tropism; D053586:Virus Internalization; D017735:Virus Latency
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011991:Receptors, Virus
keywords: CCR5; CD4; CXCR4; reservoir