Evidence map›Paper›PMID 39699169›Full record

ArticlemBio2025

The alphavirus determinants of intercellular long extension formation.

Caroline K Martin, Judy J Wan, Peiqi Yin, Thomas E Morrison, William B Messer, Vanessa Rivera-Amill, Jonathan R Lai, Nina Grau, Félix A Rey, Thérèse Couderc and 2 more

Abstract read
In one paragraph

Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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. Review
  2. Review
  3. Review
  4. 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.

Caroline K MartinDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID 0000-0001-9448-9182
Judy J WanDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Peiqi YinDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Thomas E MorrisonDepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0002-1811-2938
William B MesserDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, USA.
Vanessa Rivera-AmillPonce Health Sciences University/Ponce Research Institute, Ponce, Puerto Rico.
Jonathan R LaiDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID 0000-0002-4863-0015
Nina GrauInstitut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
Félix A ReyInstitut Pasteur, Université Paris Cité, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.ORCID 0000-0002-9953-7988
Thérèse CoudercInstitut Pasteur, Université Paris Cité, Inserm U1117, Biology of Infection Unit, Paris, France.
Marc LecuitInstitut Pasteur, Université Paris Cité, Inserm U1117, Biology of Infection Unit, Paris, France.
Margaret KielianDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID 0000-0002-7395-4791

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
Molecular Analysis of Alphavirus Membrane Fusion ProteinR01AI075647 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KIELIAN, MARGARET · 2007 to 2023
$9.0M
MOLECULAR MECHANISMS OF ALPHAVIRUS ENTRY AND EXITR01GM057454 · NIGMS · YESHIVA UNIVERSITY · PI KIELIAN, MARGARET · 1999 to 2020
$7.2M
Engineered, multispecific antibodies as broad anti-filovirus therapeuticsR01AI125462 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI LAI, JONATHAN R. · 2017 to 2020
$3.0M
Flavivirus immunity in endemic and non-endemic human cohortsR01AI153434 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI MESSER, WILLIAM · 2021 to 2025
$2.3M
Clearance of Blood-Borne ArbovirusesR01AI148144 · NIAID · UNIVERSITY OF COLORADO DENVER · PI MORRISON, THOMAS E · 2020 to 2025
$2.3M
Identification and characterization of host proteins involved in the alphavirus exit pathwayR21AI166194 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI KIELIAN, MARGARET · 2021 to 2022
$462k
HHS | Centers for Disease Control and Prevention (CDC) CDK000580HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI075647HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI125462HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI148144HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI153434HHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM057454NCI NIH HHS P30 CA013330NIAID NIH HHS R01 AI075647NIAID NIH HHS R01 AI125462NIAID NIH HHS R01 AI148144NIAID NIH HHS R01 AI153434NIAID NIH HHS R21 AI166194NIGMS NIH HHS R01 GM057454
6 · The paper itself

Abstract

The alphavirus chikungunya virus (CHIKV) is a serious human pathogen that can cause large-scale epidemics characterized by fever and joint pain and often resulting in chronic arthritis. Infection by alphaviruses including CHIKV and the closely related Semliki Forest virus (SFV) can induce the formation of filopodia-like intercellular long extensions (ILEs). ILEs emanate from an infected cell, stably attach to a neighboring cell, and mediate cell-to-cell viral transmission that is resistant to neutralizing antibodies. However, our mechanistic understanding of ILE formation is limited, and the potential contribution of ILEs to CHIKV virulence or human CHIKV infection is unknown. Here, we used well-characterized virus mutants and monoclonal antibodies with known epitopes to dissect the virus requirements for ILE formation. Our results showed that both the viral E2 and E1 envelope proteins were required for ILE formation, while viral proteins 6K and transframe, and cytoplasmic nucleocapsid formation were dispensable. A subset of CHIKV monoclonal antibodies reduced ILE formation by masking specific regions particularly on the E2 A domain. Studies of the viral proteins from different CHIKV strains showed that ILE formation is conserved across the four major CHIKV lineages. Sera from convalescent human CHIKV patients inhibited ILE formation in cell culture, providing the first evidence for ILE inhibitory antibody production during human CHIKV infections.IMPORTANCEChikungunya virus (CHIKV) infections can cause severe fever and long-lasting joint pain in humans. CHIKV is disseminated by mosquitoes and is now found world-wide, including in the Americas, Asia, and Africa. In cultured cells, CHIKV can induce the formation of long intercellular extensions that can transmit virus to another cell. However, our understanding of the formation of extensions and their importance in human CHIKV infection is limited. We here identified viral protein requirements for extension formation. We demonstrated that specific monoclonal antibodies against the virus envelope proteins or sera from human CHIKV patients can inhibit extension formation. Our data highlight the importance of evaluation of extension formation in the context of human CHIKV infection.

Indexed as

Chikungunya virusViral Envelope ProteinsAnimalsAntibodies, MonoclonalCell LineChikungunya FeverChlorocebus aethiopsHumansSemliki forest virusVero CellsAntibodies, MonoclonalViral Envelope Proteinsalphaviruschikungunyaintercellular transmissionvirus buddingvirus exit

Identifiers

PMID39699169
PMCPMC11796390

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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.