HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effect of point mutations in the N terminus of the lentivirus lytic peptide-1 sequence of human immunodeficiency virus type 1 transmembrane protein gp41 on Env stability.

Abstract
To understand the role of the lentivirus lytic peptide-1 region of the human immunodeficiency virus type 1 transmembrane glycoprotein (gp) 41 in viral infection, we examined the effects on virus replication of single amino acid deletions spanning this region in an infectious provirus of the HXB2 strain. Among the mutants analyzed, only the deletion of one of the two adjacent valine residues located at positions 832 and 833 (termed the Delta 833 mutant for simplicity) greatly reduced the steady-state, cell-associated levels of the Env precursor and gp120, as opposed to the wild-type virus. The altered Env phenotype resulted in severely impaired virus infectivity and gp120 incorporation into this mutant virion. Analyses of additional mutants with deletions at Ile-830, Ala-836, and Ile-840 demonstrated that the Delta 830 mutant exhibited the most significant inhibitory effect on Env steady-state expression. These results indicate that the N terminus of the lentivirus lytic peptide-1 region is critical for Env steady-state expression. Among the mutant viruses encoding Env proteins in which residues Val-832 and Val-833 were individually substituted by nonconserved amino acids Ala, Ser, or Pro, which were expected to disrupt the alpha-helical structure in the increasingly severe manner of Pro > Ser > Ala, only the 833P mutant exhibited significantly reduced steady-state Env expression. Pulse labeling and pulse-chase studies demonstrated that the Delta 830, Delta 833, and 833P mutants of Env proteins degraded more rapidly in a time-dependent manner after biosynthesis than did the wild-type Env. The results indicate that residue 830 and 833 mutations are likely to induce a conformational change in Env that targets the mutant protein for cellular degradation. Our study has implications about the structural determinants located at the N terminus of the lentivirus lytic peptide-1 sequence of gp41 that affect the fate of Env in virus-infected cells.
AuthorsSheau-Fen Lee, Chiung-Yuan Ko, Chin-Tien Wang, Steve S-L Chen
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 18 Pg. 15363-75 (May 03 2002) ISSN: 0021-9258 [Print] United States
PMID11859090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA Primers
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • lentiviral lytic peptide type 1, Human immunodeficiency virus 1
  • Valine
Topics
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Genes, env
  • HIV Envelope Protein gp41 (chemistry, genetics)
  • HIV-1 (genetics, pathogenicity, physiology)
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptide Fragments (genetics)
  • Phenotype
  • Point Mutation
  • Sequence Deletion
  • Valine
  • Virulence
  • Virus Replication

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: