Document Detail

Replication of HIV-1 viruses in the presence of the Portland alpha1-antitrypsin variant (alpha1-PDX) inhibitor.
MedLine Citation:
PMID:  11695999     Owner:  NLM     Status:  MEDLINE    
The Portland alpha1-antitrypsin variant (alpha1-PDX) inhibits gp160 cleavage into gp120 and gp41 by different prohormone convertases (PCs) including furin, PC5 and PC7. Jurkat cells stably transfected with this inhibitor (J-PDX cells) and, as controls, Jurkat cells transfected with the empty vector (J-pcDNA3) were tested for their susceptibility to HIV-1 infection. We found that HIV-1 replication was significantly impaired in J-PDX cells. However, the analysis of the infectivity of HIV-1 viruses produced in J-PDX cells on different days during the infection indicated that they recovered infectivity starting from 13 days post-infection. The sequencing of viruses collected earlier and later from J-PDX cells revealed no mutations in envelope-glycoprotein precursor (Env) maturation sites or in the N-terminal sequence of gp41 fusion peptide, which plays a key role in membrane fusion. Although conserved mutations were detected at the C-terminus of the gp41 fusion peptide and ectodomain, the replication of mutant HIV-1 viruses produced on day 20 in J-PDX cells was inhibited at a similar level to wild-type viruses after a second passage in J-PDX cells. We then investigated the expression of the alpha1-PDX protein, and found that HIV-1 replication activated its proteolysis since the 54 kDa cleaved form became predominant later on in the infection. In contrast, the expression of PC7, a protein that is transported through the secretory pathway, was unaltered in HIV-1 infected cells. We conclude that recovered HIV-1 infectivity in J-PDX cells was due to a loss of alpha1-PDX activity via its extensive processing by intracellular proteases that cleave it through the substrate pathway.
B Bahbouhi; N G Seidah; E Bahraoui
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  360     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-06     Completed Date:  2001-12-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  127-34     Citation Subset:  IM    
Laboratoire d'immuno-virologie, EA 30-38 Université Paul Sabatier, UFR/SVT, 31062 Toulouse, France.
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MeSH Terms
Blotting, Western
CD4-Positive T-Lymphocytes
Conserved Sequence
HIV Envelope Protein gp120 / metabolism
HIV Envelope Protein gp160 / metabolism
HIV Envelope Protein gp41 / metabolism
HIV-1 / physiology*
Jurkat Cells
Peptides / chemistry
Recombinant Fusion Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Virus Replication*
alpha 1-Antitrypsin / pharmacology*
Reg. No./Substance:
0/HIV Envelope Protein gp120; 0/HIV Envelope Protein gp160; 0/HIV Envelope Protein gp41; 0/Peptides; 0/Recombinant Fusion Proteins; 0/alpha 1-Antitrypsin; 0/alpha 1-antitrypsin Portland

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