Enhancement of human immunodeficiency virus type 1 (HIV-1) infection via increased membrane fluidity by a cationic polymer.
Cationic polymers are known to have potent activity against bacteria, but their effects on viral activity have been little studied. We investigated the effect of one such polymer, polyethyleneimine (PEI), on HIV-1 infection. Although virus-cell binding was significantly inhibited by PEI, HIV-1 infection in human T-cell lines such as MT-4 and MOLT-4 was accelerated conversely when the drug treatment was carried out, after the virus had attached to the cells or PEI was simultaneously added to the virus and cell culture system. This paradoxical effect of PEI on HIV-1 infection was examined using HIV-1 chronically infected cells (MOLT-4/HIV-1). Dissociation of the glycoprotein gp120 (as revealed by exposure of transmembrane protein gp41) from MOLT-4/HIV-1 cells and the resultant fusion of these cells was shown to be induced by the addition of PEI. Accordingly, it was suggested that the binding inhibition of HIV-1 to CD4-positive cells by PEI was due to the shedding of gp120 from HIV-1 particles, and this PEI rather promoted membrane fusion between the virus and cells leading to the enhancement of HIV-1 infection. Similarly, dissociation of gp120 from MOLT-4/HIV-1 was also induced by sCD4. The effect of these reagents on changes in membrane fluidity was evaluated by polarization (p) measurements, and it was observed that the acceleration of membrane fluidity occurred only in the PEI system. Therefore, it is likely that PEI accelerates HIV-1 infection by facilitating virus entry into the host cells through an increase in membrane fluidity.
Owada
T
T
Department of Microbiology, Tokyo Medical and Dental University School of Medicine, Japan.
Miyashita
Y
Y
Motomura
T
T
Onishi
M
M
Yamashita
S
S
Yamamoto
N
N
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D011094:Polyethyleneimine / Q000494:pharmacology*
D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D011094:Polyethyleneimine