Date Published: September 27, 2018
Publisher: Public Library of Science
Author(s): Takayoshi Kawahara, Isamu Akiba, Megumi Sakou, Takemasa Sakaguchi, Hatsumi Taniguchi, Thomas Webster.
An influenza epidemic is still a problem despite the development of vaccines and anti-influenza drugs. Preventive measures such as handwashing are fundamental and important for counteracting influenza virus infection. In this study, we clarified the anti-influenza virus effects of surfactants, which are the main components of hand soaps for hand washing: potassium oleate (C18:1), sodium laureth sulfate (LES) and sodium lauryl sulfate (SDS). For a human influenza virus strain (H3N2), C18:1 reduced the infectivity by 4 logs or more, whereas LES and SDS reduced the infectivity by 1 log or less. Similar results were obtained when an avian influenza virus strain (H5N3) was used. The interaction between the surfactant and virus was then investigated by isothermal titration calorimetry. The LES-virus system showed a positive value of enthalpy changes (ΔH), meaning an exothermic interaction that indicated a hydrophobic interaction. In contrast, both the C18:1-virus system and the SDS-virus system showed negative values of ΔH, meaning an endothermic interaction that indicated an electrical interaction. The ΔH value of the C18:1-virus system was much higher than that of the SDS-virus system. A mixture of C18:1 and HA proteins similarly showed negative values of ΔH. These results indicate that influenza virus inactivation by a hydrophobic interaction of a surfactant with the viral envelope is insufficient to prevent infection, whereas inactivation by an electrical interaction of a surfactant with HA proteins is sufficient to prevent influenza virus infection.
Influenza virus, which belongs to the family Orthomyxoviridae, has a virus particle (virion) of ca. 100 nm in diameter. The virion is covered with an envelope composed of a lipid bilayer and inserted viral spike proteins, hemagglutinin (HA), neuraminidase (NA) and M2 ion channel proteins. One influenza virus particle is estimated to contain roughly 700 HA proteins, 200 NA proteins and 20 M2 proteins .
It is generally believed that the mechanism of influenza virus inactivation by a surfactant is fusion with the envelope membrane by a hydrophobic interaction . This is because the influenza virus surface is covered by a lipid bilayer of the envelope membrane that interacts readily with the hydrophobic group of a surfactant. Since the LES-virus system showed an endothermic interaction, a hydrophobic interaction is dominant between LES and the influenza virus. Among the three surfactants used in this study, LES showed the weakest anti-virus effect. Therefore, the efficiency of inactivation of an influenza virus by fusion of a surfactant with the envelope by a hydrophobic interaction is insufficient to prevent infection of the influenza virus. On the other hand, both the SDS-virus and C18:1-virus systems showed exothermic interactions, suggesting that electrical interactions occur between these surfactants and the influenza virus. As is well known, SDS and C18:1 are anionic surfactants. In contrast, the envelope membrane of an influenza virus is negatively charged like the lipid membrane of a cell. The hydrophilic groups of SDS and C18:1 and the envelope membrane of influenza virus are both negatively charged and therefore do not undergo an electrical interaction. Then, which portion of the influenza virus interacted with SDS and C18:1? An influenza virus has spike proteins, including HA, NA and M2, protruding from the envelope. Among these, the HA protein is the major population and tends to be positively charged [12, 13]. It is therefore considered that the hydrophilic groups of SDS and C18:1 interacted electrostatically with the HA protein to be adsorbed to the influenza virus and inactivated the virus. Actually, the interaction between C18:1 and HA has been shown to be an attractive interaction (S1 Fig). Furthermore, since the absolute value of ΔH of the C18:1-virus is much higher than that of the SDS-virus, the electrostatic interaction between C18:1 and HA is much stronger than that of the SDS-virus. C18:1 showed a stronger anti-virus effect than that of SDS. SDS has sulfonic acid as the hydrophilic group and has a large ionic radius. On the other hand, C18:1 has carboxylic acid as the hydrophilic group and has a smaller ionic radius than that of SDS. This means that the repulsion of C18:1 against the envelope membrane of the influenza virus is weaker than that of SDS. Accordingly, C18:1 could approach the virus surface more easily in comparison with SDS. It is therefore considered that electrostatic interaction could interact electrically with HA more readily than could SDS. C18:1 is thus thought to exhibit a stronger exothermic interaction and consequently show a stronger anti-virus effect than that of SDS.