Effect of Envelope Proteins on the Mechanical Properties of Influenza Virus

• Published in: The Journal of biological chemistry Vol. 287; no. 49; pp. 41078 - 41088
• Main Authors: Schaap, Iwan A.T., Eghiaian, Frédéric, des Georges, Amédée, Veigel, Claudia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-11-2012; American Society for Biochemistry and Molecular Biology
• Subjects: Atomic Force Microscopy; Biophysics - methods; Capsid - chemistry; Cryoelectron Microscopy - methods; Electrons; Hydrogen-Ion Concentration; Influenza Virus; Kinetics; Light; Lipid Bilayers - chemistry; Lipids - chemistry; Liposomes; Liposomes - chemistry; Membrane Biophysics; Micelles; Microscopy, Atomic Force - methods; Molecular Biophysics; Orthomyxoviridae - metabolism; Particle Size; Scattering, Radiation; Stress, Mechanical; Viral Envelope Proteins - chemistry; Virus; Virus; Influenza Virus; Membrane Biophysics; Atomic Force Microscopy; Liposomes
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.412726

The envelope of the influenza virus undergoes extensive structural change during the viral life cycle. However, it is unknown how lipid and protein components of the viral envelope contribute to its mechanical properties. Using atomic force microscopy, here we show that the lipid envelope of spherical influenza virions is ∼10 times softer (∼0.05 nanonewton nm−1) than a viral protein-capsid coat and sustains deformations of one-third of the virion's diameter. Compared with phosphatidylcholine liposomes, it is twice as stiff, due to membrane-attached protein components. We found that virus indentation resulted in a biphasic force-indentation response. We propose that the first phase, including a stepwise reduction in stiffness at ∼10-nm indentation and ∼100 piconewtons of force, is due to mobilization of membrane proteins by the indenting atomic force microscope tip, consistent with the glycoprotein ectodomains protruding ∼13 nm from the bilayer surface. This phase was obliterated for bromelain-treated virions with the ectodomains removed. Following pH 5 treatment, virions were as soft as pure liposomes, consistent with reinforcing proteins detaching from the lipid bilayer. We propose that the soft, pH-dependent mechanical properties of the envelope are critical for the pH-regulated life cycle and support the persistence of the virus inside and outside the host.
Background: The lipid and protein contributions to the mechanical properties of the influenza viral envelope are unknown.
Results: The influenza viral envelope is 10 times softer than a viral protein-capsid coat but stiffer than a liposome.
Conclusion: Membrane-associated proteins contribute to the mechanical stiffness of the viral envelope.
Significance: The mechanical properties of the envelope are critical for the viral pH-regulated life cycle.