A peptide inhibitor of human immunodeficiency virus infection binds to novel human cell surface polypeptides.
Putative cell surface human immunodeficiency virus (HIV) gp41 receptor proteins of 45 and 80 kDa (p45 and p80, respectively) were identified on human cells using a 17-amino acid peptide, referred to as CS3. In contrast, murine P815 cells expressed a peptide binding protein of 80 kDa only. A segment of 8 amino acids within CS3 contains the minimum sequence able to inhibit binding of radiolabeled CS3 to p80 and p45, as shown by competitive binding studies. Human p45 was purified from CD4+ RH9 cells by CS3 peptide affinity chromatography. Human p80 was partially purified from RH9 cell lysates by size exclusion chromatography followed by SDS-polyacrylamide gel electrophoresis; a rabbit polyclonal antibody was raised against this preparation. Anti-p80 antibody inhibited HIV infection in a dose-dependent manner. The CS3 region of gp41 has been been shown previously to be exposed on viral particles and envelope-expressing cells predominately after conformational changes in the HIV envelope occur due to the interaction of CD4 with gp120. These results, together with those from previous studies, suggest that following the interaction of gp120 with CD4, there may be a second receptor interaction necessary for virus entry/fusion.
Henderson
L A
LA
Guthrie Research Institute, Sayre, Pennsylvania 18840.
Qureshi
M N
MN
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D015728:Receptors, HIV / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; D000998:Antiviral Agents; D015704:CD4 Antigens; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D015728:Receptors, HIV; D012709:Serum Albumin