Alterations of lymphocyte membranes during HIV-1 infection via multiple and simultaneous entry strategies.
Human immunodeficiency virus type 1 (HIV-1) must bind to and enter lymphocytes to replicate and cause the acquired immunodeficiency syndrome. The association of viral particles with the lymphocyte plasma membrane may vary according to a multitude of unknown variables, including lymphocyte membrane receptor mobilization, lipid raft aggregation, clathrin, caveolin, endosomes, microendosome-mediated penetration or penetration through a hole in the membrane. The time course of this delivery appears to be short. Fusion of the virion membrane and lymphocyte plasma membrane leads to destabilization of the lymphocyte membrane. Five morphological stages of membrane alteration were observed in the infected lymphocytes: (1) swelling, (2) splitting, (3) fusion, (4) breaking, and (5) thinning of the lipid bilayer. These plasma membrane alterations were not contributed by fixation artifacts, because the dimensions and distance between the subunits of the surface glycoprotein (SU, gp120) and the transmembrane glycoprotein (gp41) of the viral particles adjacent to the infected cells and processed at the same time remained unchanged. Destabilization of lipid raft patches in the lymphocyte plasma membrane by unknown variables may facilitate HIV-1 penetration of lymphocyte, and other cell types. This a combined review of the pertinent literature with our data showing that HIV-1 may take advantage of multiple penetration approaches simultaneously in the same cell type (H9) to overwhelm the infected cells. The ultrastructural details of H9 cultured cells infected in vitro with HIV-1 contribute to our understanding of viral particle association with the plasma membrane of infected cells.
Fermin
Cesar
C
Ultrastructural Pathology Unit, Tulane University Health Sciences Center, New Orleans, Louisiana, USA. cfermin@tulane.edu
Garry
Robert
R
D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism
D008051:Lipid Bilayers