Evidence map›Paper›PMID 25421818›Full record

ArticleRetrovirology2014

HIV-2 interaction with cell coreceptors: amino acids within the V1/V2 region of viral envelope are determinant for CCR8, CCR5 and CXCR4 usage.

Quirina Santos-Costa, Maria Manuel Lopes, Marta Calado, José Miguel Azevedo-Pereira

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-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

6 citing papers in PubMed, 12 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

4 authors at 1 institution in 1 country.

Quirina Santos-CostaHost-Pathogen Interaction Unit, Research Institute for Medicines and Pharmaceutical Sciences (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal. quirina.c@ff.ul.pt.
Maria Manuel LopesCentro de Patogénese Molecular, Unidade dos Retrovírus e Infecções Associadas (CPM-URIA), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal. mlopes@ff.ul.pt.
Marta CaladoHost-Pathogen Interaction Unit, Research Institute for Medicines and Pharmaceutical Sciences (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal. mrtcalado@ff.ul.pt.
José Miguel Azevedo-PereiraHost-Pathogen Interaction Unit, Research Institute for Medicines and Pharmaceutical Sciences (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal. miguel.pereira@ff.ul.pt.
University of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman immunodeficiency virus 1 and 2 (HIV-1 and HIV-2) use cellular receptors in distinct ways. Besides a more promiscuous usage of coreceptors by HIV-2 and a more frequent detection of CD4-independent HIV-2 isolates, we have previously identified two HIV-2 isolates (HIV-2MIC97 and HIV-2MJC97) that do not use the two major HIV coreceptors: CCR5 and CXCR4. All these features suggest that in HIV-2 the Env glycoprotein subunits may have a different structural organization enabling distinct - although probably less efficient - interactions with cellular receptors.

resultsBy infectivity assays using GHOST cell line expressing CD4 and CCR8 and blocking experiments using CCR8-specific ligand, I-309, we show that efficient replication of HIV-2MIC97 and HIV-2MJC97 requires the presence of CCR8 at plasma cell membrane. Additionally, we disclosed the determinants of chemokine receptor usage at the molecular level, and deciphered the amino acids involved in the usage of CCR8 (R8 phenotype) and in the switch from CCR8 to CCR5 or to CCR5/CXCR4 usage (R5 or R5X4 phenotype). The data obtained from site-directed mutagenesis clearly indicates that the main genetic determinants of coreceptor tropism are located within the V1/V2 region of Env surface glycoprotein of these two viruses.

conclusionsWe conclude that a viral population able to use CCR8 and unable to infect CCR5 or CXCR4-positive cells, may exist in some HIV-2 infected individuals during an undefined time period, in the course of the asymptomatic stage of infection. This suggests that in vivo alternate molecules might contribute to HIV infection of natural target cells, at least under certain circumstances. Furthermore we provide direct and unequivocal evidence that the usage of CCR8 and the switch from R8 to R5 or R5X4 phenotype is determined by amino acids located in the base and tip of V1 and V2 loops of HIV-2 Env surface glycoprotein.

Indexed as

Virus AttachmentAdultAmino AcidsCell LineDNA Mutational Analysisenv Gene Products, Human Immunodeficiency VirusHIV-2HumansMutagenesis, Site-DirectedReceptors, CCR5Receptors, CCR8Receptors, CXCR4Receptors, HIVVirus ReplicationAmino AcidsCCR5 protein, humanCCR8 protein, humanCXCR4 protein, humanenv Gene Products, Human Immunodeficiency VirusReceptors, CCR5Receptors, CCR8Receptors, CXCR4Receptors, HIV

Identifiers

PMID25421818
PMCPMC4251929
OpenAlexW2161773153

What OpenQuestion holds

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LicenceCC BY
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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.