Blocking of human immunodeficiency virus type-1 virion autolysis by autologous p2(gag) peptide

Shogo Misumi; Yukimi Morikawa; Mitsunori Tomonaga; Kouichi Ohkuma; Nobutoki Takamune; Shozo Shoji

doi:10.1093/jb/mvh052

Blocking of human immunodeficiency virus type-1 virion autolysis by autologous p2(gag) peptide

J Biochem. 2004 Mar;135(3):447-53. doi: 10.1093/jb/mvh052.

Authors

Shogo Misumi¹, Yukimi Morikawa, Mitsunori Tomonaga, Kouichi Ohkuma, Nobutoki Takamune, Shozo Shoji

Affiliation

¹ Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.

PMID: 15113844
DOI: 10.1093/jb/mvh052

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Amino Acid Substitution / genetics
Animals
Antibody Specificity
Autolysis / virology*
Cell Line
Female
Gene Products, gag / chemistry
Gene Products, gag / genetics
Gene Products, gag / metabolism
Gene Products, gag / pharmacology*
Gene Products, tat / genetics
Gene Products, tat / metabolism
HIV Core Protein p24 / metabolism
HIV Protease / metabolism
HIV Protease Inhibitors / pharmacology
HIV-1 / drug effects*
HIV-1 / physiology*
Humans
Mice
Mutation / genetics
Oligopeptides / chemistry
Oligopeptides / genetics
Oligopeptides / pharmacology*
Peptide Fragments / chemistry
Peptide Fragments / genetics
Peptide Fragments / metabolism
Peptide Fragments / pharmacology*
Protein Precursors / chemistry
Protein Precursors / genetics
Protein Precursors / metabolism
Protein Processing, Post-Translational / drug effects
Protein Processing, Post-Translational / physiology
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Virion / drug effects*
Virion / physiology*
gag Gene Products, Human Immunodeficiency Virus
tat Gene Products, Human Immunodeficiency Virus

Substances

Gene Products, gag
Gene Products, tat
HIV Core Protein p24
HIV Protease Inhibitors
Oligopeptides
Peptide Fragments
Protein Precursors
Recombinant Fusion Proteins
gag Gene Products, Human Immunodeficiency Virus
p2 gag peptide, Human immunodeficiency virus 1
p55 gag precursor protein, Human immunodeficiency virus 1
tat Gene Products, Human Immunodeficiency Virus
HIV Protease