Evidence map›Paper›PMID 40408432›Full record

ArticlePLoS pathogens2025

Transmitted/founder (T/F) HIV-1 derived from sexual contact exhibits greater transmission fitness in human cervical tissue than T/F HIV-1 from blood-to-blood contact: Unique glycan profiles on T/F envelopes associated with transmission phenotypes.

Yiying Zhang, Katja Klein, Annette Ratcliff, Sashini Loku Galappaththi, Nicholas Hathaway, Nicholas Twells, Mukti Patel, Stephen Temesy, Jeffrey A Bailey, Lara K Mahal and 2 more

Erratum issuedAbstract read
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In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Yiying ZhangDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.
Katja KleinDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.
Annette RatcliffDepartment of Molecular Biology and Microbiology and Division of Infectious Diseases, Case Western Reserve University, Cleveland, United States of America.
Sashini Loku GalappaththiDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.
Nicholas HathawayDepartment of Pathology and Laboratory Medicine, Brown University, Providence, United States of America.
Nicholas TwellsDepartment of Chemistry, University of Alberta, Edmonton, Canada.
Mukti PatelDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.
Stephen TemesyDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.
Jeffrey A BaileyDepartment of Pathology and Laboratory Medicine, Brown University, Providence, United States of America.
Lara K MahalDepartment of Chemistry, University of Alberta, Edmonton, Canada.
Carole CreuzenetDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.
Eric J ArtsDepartment of Microbiology and Immunology, University of Western Ontario, London, Canada.ORCID 0000-0002-4880-7968

Funding

Impact of HIV-1 Fitness on Disease ProgressionR01AI049170 · NIAID · UNIVERSITY OF WESTERN ONTARIO · PI ARTS, ERIC J · 2002 to 2024
$6.8M
HIV-1 Fitness and RecombinationR56AI049170 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ARTS, ERIC J · 2012 to 2012
$400k
Impact of HIV-1 Fitness on Disease ProgressionR21AI049170 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ARTS, ERIC J · 2001 to 2001
$265k
NIAID NIH HHS R01 AI049170NIAID NIH HHS R21 AI049170NIAID NIH HHS R56 AI049170
6 · The paper itself

Abstract

Human immunodeficiency virus 1 (HIV-1) risk groups include, but are not limited to, heterosexual individuals (HET), men-who-have-sex-with-men (MSM), and people who inject drugs (PWID). Although genetically diverse HIV-1 populations are transferred from donor to recipient, systemic infection is often established by a single clone, the transmitted/founder (T/F) virus. This phenomenon is especially prevalent in sexual transmission, but less stringent in blood-to-blood contact transmission. Specific traits that permit successful transmission have not been well characterized. Thus, HIV-1 containing the chimeric T/F envelope (Env) from different transmission routes was assessed for ex vivo transmission fitness by performing mixed competition assays (also referred to as mixed competitions) on human cervical tissues. We found that chimeric T/F viruses isolated from the PWID exhibit limited replication capacity in cervical tissues when compared to those from MSM and HET, diminishing their chances of transmission to T helper type 1 (Th1) and Th17 cells. This reduced transmission fitness of T/F HIV-1 from PWID was not observed when infecting Th1 and Th17 cells directly, bypassing cervical tissues. Phenotypic assays showed that the chimeric T/F viruses from PWID differed from other groups by having an enhanced ability to utilize diverse CCR5 conformations, while Env expression level, CD4/CCR5 utilization, and entry speed did not differ. Different glycosylation profiles were detected on T/F compared to chronic Env with increased complex, fucosylated N- and O-glycans found more frequently on the T/F Env. Furthermore, the increased presence of these fucosylated glycans correlated with replication fitness in cervical tissues. In contrast, bisecting branched N-glycan found more frequently on chronic Env was associated with decreased entry efficiency and more stringent usage of CCR5. These findings suggest that glycosylation patterns/levels and/or Env structure greatly impact the differences in transmission fitness of T/F HIV-1.

Indexed as

Cervix Uterienv Gene Products, Human Immunodeficiency VirusHIV-1HIV InfectionsPolysaccharidesFemaleHumansMalePhenotypeenv Gene Products, Human Immunodeficiency VirusPolysaccharides

Identifiers

PMID40408432
PMCPMC12140434

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LicenceCC BY
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Registered trials

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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.