Evidence map›Paper›PMID 11861826›Full record

ArticleJournal of virology2002

Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins.

James M Binley, Rogier W Sanders, Aditi Master, Charmagne S Cayanan, Cheryl L Wiley, Linnea Schiffner, Bruce Travis, Shawn Kuhmann, Dennis R Burton, Shiu-Lok Hu and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
1.5field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 150 citations in OpenAlex.

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  19. Article
  20. Development of a RPLC-UV method for monitoring uncleaved HIV-1 envelope glycoprotein.Analytical methods : advancing methods and applications · 2021
    Article

49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

James M BinleyDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA. jbinley@scripps.edu
Rogier W Sanders
Aditi Master
Charmagne S Cayanan
Cheryl L Wiley
Linnea Schiffner
Bruce Travis
Shawn Kuhmann
Dennis R Burton
Shiu-Lok Hu
William C Olson
John P Moore
Cornell University · USProgenics Pharmaceuticals (United States) · USScripps Research Institute · USUniversity of Washington · USUniversity of Amsterdam · NL

Funding

MODIFIED ENVELOPE GLYCOPROTEINS FOR HIV1 VACCINER01AI045463 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1999 to 2010
$4.2M
HIV Vaccine Design and Development TeamR01AI049764 · NIAID · PROGENICS PHARMACEUTICALS, INC. · PI MADDON, PAUL J · 2000 to 2001
$4.1M
DETERMINANTS OF VACCINE PROTECTION IN A SIV MODELR01AI047735 · NIAID · UNIVERSITY OF WASHINGTON · PI HU, SHIU-LOK · 2000 to 2005
$2.4M
STABILIZING ENV IN VIRUS-LIKE PARTICLE IMMUNOGENSR21AI049566 · NIAID · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI BINLEY, JAMES M · 2000 to 2001
$520k
NIAID NIH HHS AI45463NIAID NIH HHS AI47735NIAID NIH HHS AI49566NIAID NIH HHS AI49764NIAID NIH HHS R01 AI045463NIAID NIH HHS R01 AI047735
6 · The paper itself

Abstract

In virus-infected cells, the envelope glycoprotein (Env) precursor, gp160, of human immunodeficiency virus type 1 is cleaved by cellular proteases into a fusion-competent gp120-gp41 heterodimer in which the two subunits are noncovalently associated. However, cleavage can be inefficient when recombinant Env is expressed at high levels, either as a full-length gp160 or as a soluble gp140 truncated immediately N-terminal to the transmembrane domain. We have explored several methods for obtaining fully cleaved Env for use as a vaccine antigen. We tested whether purified Env could be enzymatically digested with purified protease in vitro. Plasmin efficiently cleaved the Env precursor but also cut at a second site in gp120, most probably the V3 loop. In contrast, a soluble form of furin was specific for the gp120-gp41 cleavage site but cleaved inefficiently. Coexpression of Env with the full-length or soluble form of furin enhanced Env cleavage but also reduced Env expression. When the Env cleavage site (REKR) was mutated in order to see if its use by cellular proteases could be enhanced, several mutants were found to be processed more efficiently than the wild-type protein. The optimal cleavage site sequences were RRRRRR, RRRRKR, and RRRKKR. These mutations did not significantly alter the capacity of the Env protein to mediate fusion, so they have not radically perturbed Env structure. Furthermore, unlike that of wild-type Env, expression of the cleavage site mutants was not significantly reduced by furin coexpression. Coexpression of Env cleavage site mutants and furin is therefore a useful method for obtaining high-level expression of processed Env.

Indexed as

EndopeptidasesFurinGene Products, envHeLa CellsHIV-1HIV Envelope Protein gp120HIV Envelope Protein gp160HIV Envelope Protein gp41HumansProtein PrecursorsRecombinant ProteinsSubtilisinsEndopeptidasesFurinGene Products, envHIV Envelope Protein gp120HIV Envelope Protein gp160HIV Envelope Protein gp41Protein PrecursorsRecombinant ProteinsSubtilisins

Identifiers

PMID11861826
PMCPMC135977
OpenAlexW2038879287

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.