Evidence map›Paper›PMID 12208966›Full record

ArticleJournal of virology2002

Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein.

Shi-Hua Xiang, Peter D Kwong, Rishi Gupta, Carlo D Rizzuto, David J Casper, Richard Wyatt, Liping Wang, Wayne A Hendrickson, Michael L Doyle, Joseph Sodroski

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 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

126 citing papers in PubMed, 185 citations in OpenAlex.

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66 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

10 authors at 4 institutions in 1 country.

Shi-Hua XiangDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Harvard Medical School. Boston, Massachusetts 02115, USA.
Peter D Kwong
Rishi Gupta
Carlo D Rizzuto
David J Casper
Richard Wyatt
Liping Wang
Wayne A Hendrickson
Michael L Doyle
Joseph Sodroski
Harvard University · USDana-Farber Cancer Institute · USGlaxoSmithKline (United States) · USHoward Hughes Medical Institute · US

Funding

HIV-1 ENVELOPE GLYCOPROTEINSR37AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1996 to 2015
$11.6M
CORE--VIROLOGYP30AI042848 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LUBAN, JEREMY · 1998 to 2002
$4.3M
MOLECULAR STUDIES OF HIV1 NEUTRALIZING ANTIBODIESR01AI031783 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1991 to 2007
$2.9M
MOLECULAR INTERACTION BETWEEN HIV1 GP120-CD4 COMPLEXESR01AI041851 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1997 to 2006
$2.8M
MONOCLONAL ANTIBODIES TO HIV-1 GP 120R01AI024030 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ROBINSON, JAMES E · 1987 to 2005
$1.5M
Design Of ImmunogensZ01AI005024 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI KWONG, PETER D · 2002 to 2008
$564k
ROLE OF THE HTLV-III ENVELOPE GLYCOPROTEIN IN VIRUSR01AI024755 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1987 to 1995
–
NIAID NIH HHS AI24030NIAID NIH HHS AI24755NIAID NIH HHS AI31783NIAID NIH HHS AI41815NIAID NIH HHS AI42848NIAID NIH HHS P30 AI042848NIAID NIH HHS R01 AI024030NIAID NIH HHS R01 AI031783NIAID NIH HHS R01 AI041851NIAID NIH HHS R37 AI024755
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein is conformationally flexible. Upon binding to the host cell receptor CD4, gp120 assumes a conformation that is recognized by the second receptor, CCR5 and/or CXCR4, and by the CD4-induced (CD4i) antibodies. Guided by the X-ray crystal structure of a gp120-CD4-CD4i antibody complex, we introduced changes into gp120 that were designed to stabilize or disrupt this conformation. One mutant, 375 S/W, in which the tryptophan indole group is predicted to occupy the Phe 43 cavity in the gp120 interior, apparently favors a gp120 conformation closer to that of the CD4-bound state. The 375 S/W mutant was recognized as well as or better than wild-type gp120 by CD4 and CD4i antibodies, and the large decrease in entropy observed when wild-type gp120 bound CD4 was reduced for the 375 S/W mutant. The recognition of the 375 S/W mutant by CD4BS antibodies, which are directed against the CD4-binding region of gp120, was markedly reduced compared with that of the wild-type gp120. Compared with the wild-type virus, viruses with the 375 S/W envelope glycoproteins were resistant to neutralization by IgG1b12, a CD4BS antibody, were slightly more sensitive to soluble CD4 neutralization and were neutralized more efficiently by the 2G12 antibody. Another mutant, 423 I/P, in which the gp120 bridging sheet was disrupted, did not bind CD4, CCR5, or CD4i antibodies, even though recognition by CD4BS antibodies was efficient. These results indicate that CD4BS antibodies recognize conformations of gp120 different from that recognized by CD4 and CD4i antibodies.

Indexed as

CD4 AntigensCell LineHIV-1HIV Envelope Protein gp120HumansModels, StructuralMutagenesisProtein ConformationReceptors, CCR5Structure-Activity RelationshipThermodynamicsCD4 AntigensHIV Envelope Protein gp120Receptors, CCR5

Identifiers

PMID12208966
PMCPMC136507
OpenAlexW2116715603

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.