Evidence map›Paper›PMID 14645592›Full record

ArticleJournal of virology2003

Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences.

Mark A Jensen, Fu-Sheng Li, Angélique B van 't Wout, David C Nickle, Daniel Shriner, Hong-Xia He, Sherry McLaughlin, Raj Shankarappa, Joseph B Margolick, James I Mullins

Abstract readEvaluation Study
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
219citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

219 citing papers in PubMed, 1 synthesis or guideline pooled it.

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159 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.

Mark A JensenDepartment of Microbiology, University of Washington, Seattle, Washington 98195-8070, USA. majensen@u.washington.edu
Fu-Sheng Li
Angélique B van 't Wout
David C Nickle
Daniel Shriner
Hong-Xia He
Sherry McLaughlin
Raj Shankarappa
Joseph B Margolick
James I Mullins

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Early in infection, human immunodeficiency virus type 1 (HIV-1) generally uses the CCR5 chemokine receptor (along with CD4) for cellular entry. In many HIV-1-infected individuals, viral genotypic changes arise that allow the virus to use CXCR4 (either in addition to CCR5 or alone) as an entry coreceptor. This switch has been associated with an acceleration of both CD3(+) T-cell decline and progression to AIDS. While it is well known that the V3 loop of gp120 largely determines coreceptor usage and that positively charged residues in V3 play an important role, the process of genetic change in V3 leading to altered coreceptor usage is not well understood. Further, the methods for biological phenotyping of virus for research or clinical purposes are laborious, depend on sample availability, and present biosafety concerns, so reliable methods for sequence-based "virtual phenotyping" are desirable. We introduce a simple bioinformatic method of scoring V3 amino acid sequences that reliably predicts CXCR4 usage (sensitivity, 84%; specificity, 96%). This score (as determined on the basis of position-specific scoring matrices [PSSM]) can be interpreted as revealing a propensity to use CXCR4 as follows: known R5 viruses had low scores, R5X4 viruses had intermediate scores, and X4 viruses had high scores. Application of the PSSM scoring method to reconstructed virus phylogenies of 11 longitudinally sampled individuals revealed that the development of X4 viruses was generally gradual and involved the accumulation of multiple amino acid changes in V3. We found that X4 viruses were lost in two ways: by the dying off of an established X4 lineage or by mutation back to low-scoring V3 loops.

Indexed as

Computational BiologyEvolution, MolecularGenotypeHIV-1HIV Envelope Protein gp120HIV InfectionsHumansMolecular Sequence DataPeptide FragmentsPhenotypePhylogenyPredictive Value of TestsReceptors, CCR5Receptors, CXCR4Sequence Analysis, DNAHIV Envelope Protein gp120HIV envelope protein gp120 (305-321)Peptide FragmentsReceptors, CCR5Receptors, CXCR4

Identifiers

PMID14645592
PMCPMC296044

What OpenQuestion holds

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Registered trials

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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.