Membrane-interactive phospholipids inhibit HIV type 1-induced cell fusion and surface gp160/gp120 binding to monoclonal antibody.
Membrane-interactive phospholipids (PLs), previously evaluated for activity against HIV-1 in vitro, are known to affect late steps in viral replication. Studies were done to determine the effects of PL analogs on post-translational processing of HIV-1 proteins, binding of viral surface gp160/gp120 to CD4 receptor, and HIV-1-induced cell fusion. Results of this investigation indicated that PL alone (1-octadecanamido-2-ethoxypropyl-rac-3-phosphocholine, CP-51) and PL-AZT conjugate (1-octadecanamido-2-ethoxypropyl-rac-3-phospho-3'- azido-3'-deoxythymidine, CP-92) have no effect on HIV-1-induced syntheses or processing of gp160/gp120, pr51, p24, or p17 (including myristoylation) in infected cells. Progeny HIV-1 particles made in CP-92-treated H9IIIB cells contained gp120, pr51, and p24; however, these virus particles had reduced capacity to bind to CD4+ cells. Both CP-51 and CP-92 inhibited syncytium (cell fusion) formation between treated HIV-1-infected cells and uninfected CD4+ cells, and, they reduced HIV-1 gp160/gp120 binding to CD4+ cells and monoclonal antibody. These results suggest that anti-HIV-1 activity of PL compounds involves alteration of cell surface membranes and viral envelopes. Phospholipid compounds are a novel class of membrane interactive compounds with potential use in blocking the spread of HIV-1 infection and pathogenesis in AIDS.
Krugner-Higby
L
L
Department of Comparative Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157-1064, USA.
Goff
D
D
Edwards
T
T
Iyer
N
N
Neufeld
J
J
Kute
T
T
Morris-Natschke
S
S
Ishaq
K
K
Piantadosi
C
C
Kucera
L S
LS
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002459:Cell Fusion / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000821:virology; D054306:Dideoxynucleotides; D015686:Gene Products, env / Q000378:metabolism*; D015483:HIV Antibodies / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000187:drug effects*; D007212:Indolizines / Q000494:pharmacology; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D010743:Phospholipids / Q000138:chemical synthesis / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism; D014771:Virion / Q000378:metabolism; D015215:Zidovudine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D054836:Indolizidines
D000911:Antibodies, Monoclonal; D054306:Dideoxynucleotides; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007212:Indolizines; D019814:Myristic Acid; D009227:Myristic Acids; D010742:Phospholipid Ethers; D010743:Phospholipids; D011498:Protein Precursors; D014764:Viral Proteins; D015215:Zidovudine; C096487:CP 51; C068368:CP 92; C037806:castanospermine; D054836:Indolizidines