Evidence map›Paper›PMID 25809903›Full record

ArticleRetrovirology2015

HIV-1 non-macrophage-tropic R5 envelope glycoproteins are not more tropic for entry into primary CD4+ T-cells than envelopes highly adapted for macrophages.

Thomas Musich, Olivia O'Connell, Maria Paz Gonzalez-Perez, Cynthia A Derdeyn, Paul J Peters, Paul R Clapham

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. 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

6 authors at 2 institutions in 1 country.

Thomas Musich
Olivia O'Connell
Maria Paz Gonzalez-Perez
Cynthia A Derdeyn
Paul J Peters
Paul R Clapham
University of Massachusetts Chan Medical School · USEmory University · US

Funding

UMASS MEDICAL CENTER FOR AIDS RESEARCHP30AI042845 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUZURIAGA, KATHERINE F · 1998 to 2012
$13.0M
Variation in HIV-1 R5 Envs: Consequences for tropism, neutralization & vaccinesP01AI082274 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LU, SHAN · 2009 to 2013
$9.7M
Role of V1V2 in HIV transmission and pathogenesisR01AI058706 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DERDEYN, CYNTHIA ANN · 2004 to 2016
$6.7M
HIV-1 R5 envelope determinants and properties that affect transmissionR01AI089334 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CLAPHAM, PAUL R · 2011 to 2015
$2.0M
Neurotropic HIV-1 Reservoirs Inside and Outside the BrainR01NS084910 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CLAPHAM, PAUL R · 2013 to 2017
$2.0M
NIAID NIH HHS AI082274NIAID NIH HHS AI089334NIAID NIH HHS AI58706NIAID NIH HHS P01 AI082274NIAID NIH HHS P30 AI042845NIAID NIH HHS R01 AI058706NIAID NIH HHS R01 AI089334NINDS NIH HHS NS084910NINDS NIH HHS R01 NS084910
6 · The paper itself

Abstract

backgroundNon-mac-tropic HIV-1 R5 viruses are predominantly transmitted and persist in immune tissue even in AIDS patients who carry highly mac-tropic variants in the brain. Non-mac-tropic R5 envelopes (Envs) require high CD4 levels for infection contrasting with highly mac-tropic Envs, which interact more efficiently with CD4 and mediate infection of macrophages that express low CD4. Non-mac-tropic R5 Envs predominantly target T-cells during transmission and in immune tissue where they must outcompete mac-tropic variants. Here, we investigated whether Env+ pseudoviruses bearing transmitted/founder (T/F), early and late disease non-mac-tropic R5 envelopes mediated more efficient infection of CD4+ T-cells compared to those with highly mac-tropic Envs.

resultsHighly mac-tropic Envs mediated highest infectivity for primary T-cells, Jurkat/CCR5 cells, myeloid dendritic cells, macrophages, and HeLa TZM-bl cells, although this was most dramatic on macrophages. Infection of primary T-cells mediated by all Envs was low. However, infection of T-cells was greatly enhanced by increasing virus attachment with DEAE dextran and spinoculation, which enhanced the three Env+ virus groups to similar extents. Dendritic cell capture of viruses and trans-infection also greatly enhanced infection of primary T-cells. In trans-infection assays, non-mac-tropic R5 Envs were preferentially enhanced and those from late disease mediated levels of T-cell infection that were equivalent to those mediated by mac-tropic Envs.

conclusionsOur results demonstrate that T/F, early or late disease non-mac-tropic R5 Envs do not preferentially mediate infection of primary CD4+ T-cells compared to highly mac-tropic Envs from brain tissue. We conclude that non-macrophage-tropism of HIV-1 R5 Envs in vitro is determined predominantly by a reduced capacity to target myeloid cells via low CD4 rather than a specific adaptation for T-cells entry that precludes macrophage infection.

Indexed as

Viral TropismVirus InternalizationCD4-Positive T-LymphocytesCells, Culturedenv Gene Products, Human Immunodeficiency VirusHIV-1HumansMacrophagesenv Gene Products, Human Immunodeficiency Virus

Identifiers

PMID25809903
PMCPMC4373511
OpenAlexW2138443097

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.