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Updated: May 19, 2026

In Vitro Disassembly of Influenza A Virus Capsids by Gradient Centrifugation
Published on: March 27, 2016
Filamentous influenza virus enters cells via macropinocytosis
Jeremy S Rossman1, George P Leser, Robert A Lamb
1Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.
Abstract:
Influenza virus is pleiomorphic, producing both spherical (100-nm-diameter) and filamentous (100-nm by 20-μm) virions. While the spherical virions are known to enter host cells through exploitation of clathrin-mediated endocytosis, the entry pathway for filamentous virions has not been determined, though the existence of an alternative, non-clathrin-, non-caveolin-mediated entry pathway for influenza virus has been known for many years. In this study, we confirm recent results showing that influenza virus utilizes macropinocytosis as an alternate entry pathway. Furthermore, we find that filamentous influenza viruses use macropinocytosis as the primary entry mechanism. Virions enter cells as intact filaments within macropinosomes and are trafficked to the acidic late-endosomal compartment. Low pH triggers a conformational change in the M2 ion channel protein, altering membrane curvature and leading to a fragmentation of the filamentous virions. This fragmentation may enable more-efficient fusion between the viral and endosomal membranes.
Insights
Filamentous influenza viruses primarily enter host cells via macropinocytosis, a pathway distinct from spherical virions. This process involves fragmentation within endosomes, potentially enhancing viral and endosomal membrane fusion.
Area of Science:
- Virology
- Cell Biology
- Infectious Diseases
Background:
- Influenza virus exhibits pleomorphism, with both spherical and filamentous virions.
- Spherical virions enter cells via clathrin-mediated endocytosis.
- The entry mechanism for filamentous influenza virions remained largely undetermined.
Purpose of the Study:
- To elucidate the entry pathway of filamentous influenza virus particles.
- To investigate the role of macropinocytosis in influenza virus entry.
- To understand the fate of filamentous virions post-entry.
Main Methods:
- Confirmation of influenza virus utilizing macropinocytosis.
- Observation of filamentous virion entry as intact filaments within macropinosomes.
- Analysis of virion trafficking to the late-endosomal compartment and low pH-induced changes.
Main Results:
- Filamentous influenza viruses predominantly use macropinocytosis for cell entry.
- Virions are internalized as intact filaments and trafficked to acidic endosomes.
- Low pH induces M2 ion channel conformational changes, leading to virion fragmentation.
Conclusions:
- Macropinocytosis is the primary entry route for filamentous influenza virions.
- Virion fragmentation within endosomes may facilitate viral-endosomal membrane fusion.
- This study reveals a novel entry and uncoating mechanism for pleomorphic viruses.
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