ArticleAIDS research and human retroviruses2016
Platelet Factor 4 Inhibits and Enhances HIV-1 Infection in a Concentration-Dependent Manner by Modulating Viral Attachment.
Article in AIDS research and human retroviruses, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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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.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Novel adenovirus vaccine vectors lacking thrombosis-associated interactions with platelet factor 4.iScience · 2026Article
- Platelet factor 4-derived C15 peptide broadly inhibits enteroviruses by disrupting viral attachment.Journal of virology · 2025Article
- Article
- Crosstalk between Platelets and SARS-CoV-2: Implications in Thrombo-Inflammatory Complications in COVID-19.International journal of molecular sciences · 2023Review
- Blood Platelets in Infection: The Multiple Roles of the Platelet Signalling Machinery.International journal of molecular sciences · 2023Review
- Chemokine PF4 Inhibits EV71 and CA16 Infections at the Entry Stage.Journal of virology · 2022Article
- Platelet-Released Factors: Their Role in Viral Disease and Applications for Extracellular Vesicle (EV) Therapy.International journal of molecular sciences · 2022Review
- Platelets in Viral Infections - Brave Soldiers or Trojan Horses.Frontiers in immunology · 2022Review
- Targeting SARS-CoV-2-Platelet Interactions in COVID-19 and Vaccine-Related Thrombosis.Frontiers in pharmacology · 2021Review
- Structural Features and PF4 Functions that Occur in Heparin-Induced Thrombocytopenia (HIT) Complicated by COVID-19.Antibodies (Basel, Switzerland) · 2020Review
- Platelets function as an acute viral reservoir during HIV-1 infection by harboring virus and T-cell complex formation.Blood advances · 2020Article
- Role of Platelet Cytokines in Dengue Virus Infection.Frontiers in cellular and infection microbiology · 2020Review
- Platelet factor 4 promotes rapid replication and propagation of Dengue and Japanese encephalitis viruses.EBioMedicine · 2019Article
- Human blood platelets and viruses: defense mechanism and role in the removal of viral pathogens.Thrombosis journal · 2018Review
- Platelet secretion in inflammatory and infectious diseases.Platelets · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Platelet factor 4 (PF4) has been recently shown to inhibit infection by a broad range of human immunodeficiency virus type 1 (HIV-1) isolates in vitro. We found that the inhibitory effects of PF4 are limited to a defined concentration range where PF4 exists largely in a monomeric state. Under these conditions, PF4 bound the HIV-1 envelope protein and inhibited HIV-1 attachment to the cell surface. However, as concentrations increased to the point where PF4 exists largely in tetrameric or higher-order forms, viral infection in vitro was enhanced. Enhancement could be inhibited by mutations in PF4 that shift the oligomeric equilibrium toward the monomeric state, or by using soluble glycosaminoglycans (GAGs) to which tetrameric PF4 avidly binds. We conclude that at physiologically relevant concentrations, oligomeric PF4 enhances infection by HIV-1 by interacting with the viral envelope protein as well as cell surface GAGs, enhancing virus attachment to the cell surface. This effect was not specific to HIV-1, as enhancement was seen with some but not all other viruses tested. The biphasic effects of PF4 on HIV-1 infection suggest that native PF4 will not be a useful antiviral agent and that PF4 could contribute to the hematologic abnormalities commonly seen in HIV-infected individuals by enhancing virus infection in the bone marrow.
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Registered trials
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.