Evidence map›Paper›PMID 15016843›Full record

ArticleJournal of virology2004

Amino acid 324 in the simian immunodeficiency virus SIVmac V3 loop can confer CD4 independence and modulate the interaction with CCR5 and alternative coreceptors.

Stefan Pöhlmann, Carl Davis, Silke Meister, George J Leslie, Claas Otto, Jacqueline D Reeves, Bridget A Puffer, Armin Papkalla, Mandy Krumbiegel, Andrea Marzi and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

14 citing papers in PubMed, 32 citations in OpenAlex.

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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

14 authors at 3 institutions in 2 countries.

Stefan PöhlmannDepartment of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. snpoehlm@viro.med.uni-erlangen.de
Carl Davis
Silke Meister
George J Leslie
Claas Otto
Jacqueline D Reeves
Bridget A Puffer
Armin Papkalla
Mandy Krumbiegel
Andrea Marzi
Steffen Lorenz
Jan Münch
Robert W Doms
Frank Kirchhoff
University of Pennsylvania · USUniversity Hospital Ulm · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The V3 loop of the simian immunodeficiency virus (SIV) envelope protein (Env) largely determines interactions with viral coreceptors. To define amino acids in V3 that are critical for coreceptor engagement, we functionally characterized Env variants with amino acid substitutions at position 324 in V3, which has previously been shown to impact SIV cell tropism. These changes modulated CCR5 engagement and, in some cases, allowed the efficient usage of CCR5 in the absence of CD4. The tested amino acid substitutions had highly differential effects on viral infectivity. Eleven of sixteen substitutions disrupted entry via CCR5 or the alternative coreceptor GPR15. Nevertheless, most of these variants replicated in the macaque T-cell line 221-89 and some also replicated in rhesus macaque peripheral blood monocytes, suggesting that efficient usage of CCR5 and GPR15 on cell lines is not a prerequisite for SIV replication in primary cells. Four variants showed enhanced entry into the macaque sMagi reporter cell line. However, sMagi cells did not express appreciable amounts of CCR5 and GPR15 mRNA, and entry into these cells was not efficiently blocked by a small-molecule CCR5 antagonist, suggesting that sMagi cells express as-yet-unidentified entry cofactors. In summary, we found that a single amino acid at position 324 in the SIV Env V3 loop can modulate both the efficiency and the types of coreceptors engaged by Env and allow for CD4-independent fusion in some cases.

Indexed as

Receptors, G-Protein-CoupledAmino Acid SubstitutionAnimalsCD4 AntigensCell FusionCell LineHeLa CellsHumansMacaca mulattaOrgan SpecificityProtein BindingReceptors, CCR5Receptors, PeptideReceptors, VirusSimian Immunodeficiency VirusViral Envelope ProteinsCD4 AntigensGPR15 protein, humanReceptors, CCR5Receptors, G-Protein-CoupledReceptors, PeptideReceptors, VirusViral Envelope Proteins

Identifiers

PMID15016843
PMCPMC371062
OpenAlexW2142951466

What OpenQuestion holds

Textmetadata
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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.