Evidence map›Paper›PMID 23077246›Full record

ArticleJournal of leukocyte biology2013

Macrophage-tropic HIV-1 variants from brain demonstrate alterations in the way gp120 engages both CD4 and CCR5.

Hamid Salimi, Michael Roche, Nicholas Webb, Lachlan R Gray, Kelechi Chikere, Jasminka Sterjovski, Anne Ellett, Steve L Wesselingh, Paul A Ramsland, Benhur Lee and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of leukocyte biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. CNS Macrophages and Infant Infections.Frontiers in immunology · 2020
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. HIV-1 target cells in the CNS.Journal of neurovirology · 2015
    Review
  17. Review
  18. Article
  19. Article
  20. Article
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

12 authors at 4 institutions in 2 countries.

Hamid SalimiCenter for Virology, Burnet Institute, Melbourne, Victoria, Australia.
Michael Roche
Nicholas Webb
Lachlan R Gray
Kelechi Chikere
Jasminka Sterjovski
Anne Ellett
Steve L Wesselingh
Paul A Ramsland
Benhur Lee
Melissa J Churchill
Paul R Gorry
Burnet Institute · AUMonash University · AUUniversity of California, Los Angeles · USSouth Australian Health and Medical Research Institute · AU

Funding

Quantifying differential CD4 and CCR5 usage patterns amongst HIV-1/SIV strainsR21AI092218 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEE, BENHUR · 2010 to 2011
$422k
NIAID NIH HHS R21 AI092218
6 · The paper itself

Abstract

BR-derived HIV-1 strains have an exceptional ability to enter macrophages via mechanisms involving their gp120 Env that remain incompletely understood. Here, we used cell-based affinity-profiling methods and mathematical modeling to generate quantitative VERSA metrics that simultaneously measure Env-CD4 and Env-CCR5 interactions. These metrics were analyzed to distinguish the phenotypes of M-tropic and non-M-tropic CCR5-using HIV-1 variants derived from autopsy BRs and LNs, respectively. We show that highly M-tropic Env variants derived from brain can be defined by two distinct and simultaneously occurring phenotypes. First, BR-derived Envs demonstrated an enhanced ability to interact with CD4 compared with LN-derived Envs, permitting entry into cells expressing scant levels of CD4. Second, BR-derived Envs displayed an altered mechanism of engagement between CD4-bound gp120 and CCR5 occurring in tandem. With the use of epitope mapping, mutagenesis, and structural studies, we show that this altered mechanism is characterized by increased exposure of CD4-induced epitopes in gp120 and by a more critical interaction between BR-derived Envs and the CCR5 N-terminus, which was associated with the predicted presence of additional atomic contacts formed at the gp120-CCR5 N-terminus interface. Our results suggest that BR-derived HIV-1 variants with highly efficient macrophage entry adopt conformations in gp120 that simultaneously alter the way in which the Env interacts with CD4 and CCR5.

Indexed as

BrainCD4 AntigensCells, CulturedEpitope MappingHIV-1HIV Envelope Protein gp120HumansMacrophagesModels, TheoreticalReceptors, CCR5Viral TropismCD4 AntigensHIV Envelope Protein gp120Receptors, CCR5

Identifiers

PMID23077246
PMCPMC3525831
OpenAlexW1986994531

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.