Adsorption and infectivity of human immunodeficiency virus type 1 are modified by the fluidity of the plasma membrane for multiple-site binding.
Based on the assumption that fluidity of the plasma membrane and viral envelope is necessary for recruiting additional receptors and ligands to the initial attachment site for "multiple-site binding," we determined the effect of increased temperature on viral infectivity. Infection of human immunodeficiency virus type 1 (HIV-1) and a pseudotyped luciferase-expressing chimeric virus using MAGI and GHOST/CXCR4 cells showed that in 1 hr of viral adsorption the extent of virus infection and the amount of tightly adsorbed viruses depended on temperature; and that membrane fluidity increased according to increased temperature. Augmented infection was observed as post-attachment enhancement (PAE) when cells were washed and incubated at 40 C for 1 hr after viral adsorption. PAE was completely inhibited by 1 micro M of anti-CXCR4 peptide T140, and addition of T140 at 20 min resulted in a gradual loss of inhibition of PAE, indicating the need for a 30 to 40 min timelag to ensure tight multiple-site binding. These data suggest that the accumulation of gp120 and receptor complex (multiple-site binding) was needed to complete the infection. Treatments of cells with 0.05% Tween 20 or 2 micro g/ml of anti-HLA-II antibody resulted in increases or decreases, respectively, of attached viruses and the infectivity. As well, Tween 20 and anti-HLAII antibody enhanced and suppressed the fluidity of the plasma membrane, respectively. Amounts of adsorbed viruses and degrees of viral infectivity correlated with the intensity of fluidity of the plasma membrane, probably due to the formation of multiple-site binding.
Harada
Shinji
S
Department of Medical Virology, Graduate School of Medical Sciences, Kumamoto University, Japan. biodef@gpo.kumamoto-u.ac.jp
Akaike
Takaaki
T
Yusa
Keisuke
K
Maeda
Yosuke
Y
D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology*; D008561:Membrane Fusion; D019718:Receptors, CXCR4 / Q000378:metabolism
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4