title: An envelope-determined, pH-independent endocytic route of viral entry determines the susceptibility of human immunodeficiency virus type 1 (HIV-1) and HIV-2 to Lv2 restriction.
abstract: We identified a postentry restriction, termed Lv2, which determines the cellular tropism of two related human immunodeficiency virus type 2 (HIV-2) isolates and is dependent on the sequence of the capsid (CA) and envelope (Env) proteins. To explain the reliance on both CA and Env, we proposed that restrictive Envs deliver susceptible capsids to a compartment where Lv2 is active whereas nonrestrictive Envs deliver capsids into a compartment where Lv2 is either absent or less active. To test this model, we used compounds that affect endocytic pathways (ammonium chloride, bafilomycin A1, hypertonic sucrose) or lipid rafts (methyl-beta-cyclodextrin) to treat restrictive cells and show that restricted virus can be rescued from Lv2 if a lipid-raft-dependent, pH-independent endocytic pathway is inhibited. Furthermore, viral entry into HeLa/CD4 cells containing a tailless CD4 receptor, located outside lipid rafts, was fully permissive. Finally, we show that a variety of primary HIV-1 and HIV-2 viruses are susceptible to Lv2. Thus, we show that the route of entry, determined by the viral envelope, can influence cellular tropism by avoiding intracellular blocks to infection.
authors: Wohl Virion Centre, Windeyer Institute of Medical Sciences, UCL, London, UK.
authors: David
authors: D
authors: Marchant
authors: Stuart J D
authors: SJ
authors: Neil
authors: Keith
authors: K
authors: Aubin
authors: Christian
authors: C
authors: Schmitz
authors: Aine
authors: A
authors: McKnight
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D015704:CD4 Antigens; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D021962:Membrane Microdomains / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D011506:Proteins / Q000502:physiology*; D013395:Sucrose / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000502:physiology*; D014779:Virus Replication; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D015704:CD4 Antigens; D006982:Hypertonic Solutions; D018942:Macrolides; D011506:Proteins; D014759:Viral Envelope Proteins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000643:Ammonium Chloride; D013395:Sucrose; C040929:bafilomycin A1