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Updated: Jan 12, 2026
11:19
Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
Published on: May 4, 2015
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Tradeoffs in viral fitness driven by alternative entry pathways
Marc Carrascosa-Sàez1, Jérémy Dufloo1, Rafael Sanjuán1
1Institute for Integrative Systems Biology (I2SysBio), University of Valencia - CSIC, Paterna, Spain.
Mbio
|November 5, 2025
Summary
Viral entry routes impact virus fitness. Direct plasma membrane fusion accelerates spread via syncytia, while endocytosis yields higher titers. Virus interactions determine which entry strategy is favored.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Enveloped viruses utilize endocytosis or direct plasma membrane fusion for cell entry.
- Direct fusion can lead to syncytia formation, impacting viral pathogenesis.
- The evolutionary implications of these distinct entry routes are not well understood.
Purpose of the Study:
- To investigate how alternative viral entry pathways influence viral fitness and evolution.
- To compare the biological consequences of plasma membrane entry versus endocytosis using a SARS-CoV-2 spike-based system.
Main Methods:
- Engineered vesicular stomatitis virus expressing SARS-CoV-2 spike variants (Wuhan and ΔFCS).
- Compared Wuhan spike (plasma membrane entry) with ΔFCS spike (endocytic entry).
- Conducted coinfection assays and spatial segregation experiments.
Main Results:
- Plasma membrane entry (Wuhan spike) accelerated infection and spread via syncytia.
- Endocytic entry (ΔFCS spike) resulted in reduced cytotoxicity and higher viral titers.
- Wuhan spike dominated in coinfection, suppressing the ΔFCS mutant; ΔFCS was favored under spatial segregation.
Conclusions:
- Virus-virus interactions significantly shape the relative fitness of different viral entry routes.
- Social evolution theory can model these virus-virus interactions.
- Distinct entry pathways present functional trade-offs influencing viral spread and pathogenesis.
Keywords:
SARS-CoV-2furin cleavage sitesocial evolutionsyncytiaviral entry routesvirus-virus interactionsMore Related Videos
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