title: Blocking of human immunodeficiency virus type-1 virion autolysis by autologous p2(gag) peptide.
abstract: Our previous study suggested that the p2(gag) peptide, AEAMSQVTNTATIM, inhibits human immunodeficiency virus type 1 (HIV-1) protease (PR) activity in vitro. In this study, Ala substitutions (Met4Ala and Thr8Ala) and deletion of amino acid Asn9 within the nona p2(gag) peptide (AEAMSQVTN) were found to decrease the inhibitory effect on HIV-1 PR activity. Furthermore, treatment of PMA-activated latently infected T lymphocytes, ACH-2 cells, with the p2(gag) peptide (100 and 250 micro M) resulted in a decrease in the amount of p24(gag )in the resultant viral lysates derived from the cell-free supernatant. In addition, the HIV-1-Tat-p2(gag) fusion peptide was synthesized to effectively deliver the p2(gag) peptide into the cells. The fusion peptide was incorporated into chronically infected T lymphocytes, CEM/LAV-1 cells, as detected on indirect immunofluorescence analysis using anti-p2(gag) peptide monoclonal antibodies, which recognize the nona peptide (AEAMSQVTN) derived from the N-terminus of the p2(gag) peptide, and cleaved by HIV-1 PR in vitro. Treatment of CEM/LAV-1 cells with the fusion peptide also resulted in a decrease in the amount of p24(gag )in the resultant viral lysate derived from the cell-free supernatant. Taken together, these data suggest that the p2(gag) peptide consequently blocks the autolysis of HIV-1 virions for the conservation of viral species.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ohkuma
authors.forename: Nobutoki
authors.initials: N
authors.lastname: Takamune
authors.forename: Shozo
authors.initials: S
authors.lastname: Shoji
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000918:Antibody Specificity; D001329:Autolysis / Q000821:virology*; D002460:Cell Line; D005260:Female; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000187:drug effects* / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D015696:Gene Products, tat; D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C109809:p2 gag peptide, Human immunodeficiency virus 1; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus; D016333:HIV Protease