Evidence map›Paper›PMID 30691001›Full record

ArticleViruses2019

HIV-1 Fusion with CD4+ T cells Is Promoted by Proteins Involved in Endocytosis and Intracellular Membrane Trafficking.

Mariana Marin, Yulia Kushnareva, Caleb S Mason, Sumit K Chanda, Gregory B Melikyan

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
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  4. Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
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  8. Review
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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

5 authors at 3 institutions in 1 country.

Mariana MarinDepartment of Pediatric, Division of Infectious Diseases, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA. mmarin@emory.edu.
Yulia KushnarevaFunctional Genomics Center, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. yulia@lji.org.ORCID 0000-0002-1931-5390
Caleb S MasonDepartment of Pediatric, Division of Infectious Diseases, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA. cs.mason@outlook.com.
Sumit K ChandaSanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. schanda@sbpdiscovery.org.
Gregory B MelikyanDepartment of Pediatric, Division of Infectious Diseases, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, USA. gmeliki@emory.edu.ORCID 0000-0001-5385-3013
Emory University · USLa Jolla Institute for Immunology · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUSAN JANET LITTLE · 1994 to 2026
$78.4M
BIOPHYSICS OF PROTEIN-MEDIATED MEMBRANE FUSIONR01GM054787 · NIGMS · UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE · PI MELIKIAN, GREGORY B · 2000 to 2018
$6.5M
BIOPHYSICS OF PROTEIN MEDIATED MEMBRANE FUSIONR29GM054787 · NIGMS · RUSH UNIVERSITY MEDICAL CENTER · PI MELIKIAN, GREGORY B · 1996 to 1999
–
National Institute of Allergy and Infectious Diseases AI036214NIGMS NIH HHS GM054787NIGMS NIH HHS R01 GM054787
6 · The paper itself

Abstract

The HIV-1 entry pathway into permissive cells has been a subject of debate. Accumulating evidence, including our previous single virus tracking results, suggests that HIV-1 can enter different cell types via endocytosis and CD4/coreceptor-dependent fusion with endosomes. However, recent studies that employed indirect techniques to infer the sites of HIV-1 entry into CD4+ T cells have concluded that endocytosis does not contribute to infection. To assess whether HIV-1 enters these cells via endocytosis, we probed the role of intracellular trafficking in HIV-1 entry/fusion by a targeted shRNA screen in a CD4+ T cell line. We performed a screen utilizing a direct virus-cell fusion assay as readout and identified several host proteins involved in endosomal trafficking/maturation, including Rab5A and sorting nexins, as factors regulating HIV-1 fusion and infection. Knockdown of these proteins inhibited HIV-1 fusion irrespective of coreceptor tropism, without altering the CD4 or coreceptor expression, or compromising the virus' ability to mediate fusion of two adjacent cells initiated by virus-plasma membrane fusion. Ectopic expression of Rab5A in non-permissive cells harboring Rab5A shRNAs partially restored the HIV-cell fusion. Together, these results implicate endocytic machinery in productive HIV-1 entry into CD4+ T cells.

Indexed as

EndocytosisVirus InternalizationCD4-Positive T-LymphocytesCell LineHIV-1HumansIntracellular Membranesrab5 GTP-Binding ProteinsRNA, Small InterferingSorting NexinsVirus ReplicationRAB5C protein, humanrab5 GTP-Binding ProteinsRNA, Small InterferingSorting Nexinscell fusionendocytosisHIVmembrane traffickingshRNA screenvirus fusion

Identifiers

PMID30691001
PMCPMC6409670
OpenAlexW2914008306

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.