title: Novel anti-HIV therapeutics targeting chemokine receptors and actin regulatory pathways.
abstract: The human immunodeficiency virus-1 (HIV-1) infects helper CD4(+) T cells, and causes CD4(+) T-cell depletion and immunodeficiency. In the past 30 years, significant progress has been made in antiretroviral therapy, and the disease has become manageable. Nevertheless, an effective vaccine is still nowhere in sight, and a cure or a functional cure awaits discovery. Among possible curative therapies, traditional antiretroviral therapy, mostly targeting viral proteins, has been proven ineffective. It is possible that targeting HIV-dependent host cofactors may offer alternatives, both for preventing HIV transmission and for forestalling disease progression. Recently, the actin cytoskeleton and its regulators in blood CD4(+) T cells have emerged as major host cofactors that could be targeted. The novel concept that the cortical actin is a barrier to viral entry and early post-entry migration has led to the nascent model of virus-host interaction at the cortical actin layer. Deciphering the cellular regulatory pathways has manifested exciting prospects for future therapeutics. In this review, we describe the study of HIV interactions with actin cytoskeleton. We also examine potential pharmacological targets that emerge from this interaction. In addition, we briefly discuss several actin pathway-based anti-HIV drugs that are currently in development or testing.
authors.affiliation: National Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, VA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Spear
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Wu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism / Q000821:virology; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D019380:Anti-HIV Agents; D002352:Carrier Proteins; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins
keywords: Arp2/3; CD4+ T cells; HIV-1; LIMK; actin cytoskeleton; cofilin; macrophages