Document Detail


Role of the membrane-spanning domain of human immunodeficiency virus type 1 envelope glycoprotein in cell-cell fusion and virus infection.
MedLine Citation:
PMID:  18353944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The membrane-spanning domain (MSD) of the human immunodeficiency virus type 1 (HIV-1) gp41 glycoprotein is critical for its biological activity. Previous C-terminal truncation studies have predicted an almost invariant core structure of 12 amino acid residues flanked by basic amino acids in the HIV-1 MSD that function to anchor the glycoprotein in the lipid bilayer. To further understand the role of specific amino acids within the MSD core, we initially replaced the core region with 12 leucine residues and then constructed recovery-of-function mutants in which specific amino acid residues (including a GGXXG motif) were reintroduced. We show here that conservation of the MSD core sequence is not required for normal expression, processing, intracellular transport, and incorporation into virions of the envelope glycoprotein (Env). However, the amino acid composition of the MSD core does influence the ability of Env to mediate cell-cell fusion and plays a critical role in the infectivity of HIV-1. Replacement of conserved amino acid residues with leucine blocked virus-to-cell fusion and subsequent viral entry into target cells. This restriction could not be released by C-terminal truncation of the gp41 glycoprotein. These studies imply that the highly conserved core residues of the HIV Env MSD, in addition to serving as a membrane anchor, play an important role in mediating membrane fusion during viral entry.
Authors:
Liang Shang; Ling Yue; Eric Hunter
Related Documents :
17055024 - Amino acid substitutions at multiple sites within the vaccinia virus d13 scaffold prote...
9662534 - A new class of arabidopsis mutants with reduced hexadecatrienoic acid fatty acid levels.
1543504 - Effects of the flra regulatory locus on biosynthesis and excretion of amino acids in es...
16237204 - A new method for estimating nonsynonymous substitutions and its applications to detecti...
2331214 - Adaptive changes in ileal mucosal nutrient transport following colectomy and endorectal...
15985764 - Effects of the antioxidative vitamins a, c and e on liver metastasis and intrametastati...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-03-19
Journal Detail:
Title:  Journal of virology     Volume:  82     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-15     Completed Date:  2008-06-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5417-28     Citation Subset:  IM    
Affiliation:
Emory Vaccine Center, Department of Pathology and Laboratory Medicine, and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cell Line
Cell Membrane / metabolism*
Cercopithecus aethiops
Consensus Sequence
Gene Expression Regulation
HIV-1 / chemistry,  genetics,  metabolism*
Humans
Membrane Proteins / metabolism
Molecular Sequence Data
Mutation / genetics
Sequence Alignment
Viral Envelope Proteins / chemistry,  genetics,  metabolism*
Virus Internalization*
Grant Support
ID/Acronym/Agency:
P30 AI050409/AI/NIAID NIH HHS; R01 AI33319/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/Viral Envelope Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Whole-genome expression profiling reveals that inhibition of host innate immune response pathways by...
Next Document:  HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency viru...