Evidence map›Paper›PMID 16378977›Full record

ArticleJournal of virology2006

Human immunodeficiency virus type 1 coreceptor switching: V1/V2 gain-of-fitness mutations compensate for V3 loss-of-fitness mutations.

C Pastore, R Nedellec, A Ramos, S Pontow, L Ratner, D E Mosier

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

82 citing papers in PubMed, 158 citations in OpenAlex.

  1. Trial
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  4. In vivo evolution of env in SHIV-AD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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22 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

6 authors at 3 institutions in 1 country.

C PastoreThe Scripps Research Institute, Dept. of Immunology, La Jolla, CA 92037, USA.
R Nedellec
A Ramos
S Pontow
L Ratner
D E Mosier
Washington University in St. Louis · USMolecular Oncology (United States) · USScripps Research Institute · US

Funding

HIV CORECEPTOR SWITCHINGR01AI052778 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MOSIER, DONALD E · 2003 to 2010
$3.8M
PATHOGENESIS OF HUMAN IMMUNODEFICIENCY VIRUS INFECTIONR01AI024745 · NIAID · WASHINGTON UNIVERSITY · PI RATNER, LEE · 1987 to 2007
$1.5M
HIV Coreceptor SwitchingR56AI052778 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MOSIER, DONALD E · 2011 to 2011
$474k
NIAID NIH HHS AI24745NIAID NIH HHS AI52778NIAID NIH HHS R01 AI024745NIAID NIH HHS R01 AI052778NIAID NIH HHS R56 AI052778
6 · The paper itself

Abstract

Human immunodeficiency virus type 1 (HIV-1) entry into target cells is mediated by the virus envelope binding to CD4 and the conformationally altered envelope subsequently binding to one of two chemokine receptors. HIV-1 envelope glycoprotein (gp120) has five variable loops, of which three (V1/V2 and V3) influence the binding of either CCR5 or CXCR4, the two primary coreceptors for virus entry. Minimal sequence changes in V3 are sufficient for changing coreceptor use from CCR5 to CXCR4 in some HIV-1 isolates, but more commonly additional mutations in V1/V2 are observed during coreceptor switching. We have modeled coreceptor switching by introducing most possible combinations of mutations in the variable loops that distinguish a previously identified group of CCR5- and CXCR4-using viruses. We found that V3 mutations entail high risk, ranging from major loss of entry fitness to lethality. Mutations in or near V1/V2 were able to compensate for the deleterious V3 mutations and may need to precede V3 mutations to permit virus survival. V1/V2 mutations in the absence of V3 mutations often increased the capacity of virus to utilize CCR5 but were unable to confer CXCR4 use. V3 mutations were thus necessary but not sufficient for coreceptor switching, and V1/V2 mutations were necessary for virus survival. HIV-1 envelope sequence evolution from CCR5 to CXCR4 use is constrained by relatively frequent lethal mutations, deep fitness valleys, and requirements to make the right amino acid substitution in the right place at the right time.

Indexed as

Amino Acid SequenceCell LineHIV-1HIV Envelope Protein gp120HumansMolecular Sequence DataMutationReceptors, CCR5Receptors, CXCR4Receptors, HIVSequence AlignmentVirus ReplicationHIV Envelope Protein gp120Receptors, CCR5Receptors, CXCR4Receptors, HIV

Identifiers

PMID16378977
PMCPMC1346864
OpenAlexW2152026267

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.