Results showed that enveloped viruses lost infectivity dramatically (up to four orders of magnitude) due to aeration, while the nonenveloped ones did not….The authors hypothesized that enveloped viruses were likely to accumulate at the surface of droplets, where “unbalanced forces” acting on the virions may be strong enough to produce inactivation through irreversible unfolding and rearrangement of molecules.

Our prior work identified three regimes of viability and RH for IAV (W. Yang, S. Elankumaran, and L. C. Marr, submitted for publication). (i) The first relates to physiological conditions at RH close to 100%, where viability is well preserved. At RH close to 100%, evaporation is minimal, and concentrations of salts in the aerosol thus stay at levels close to physiological conditions, which are harmless to the viruses. (ii) The second involves concentrated conditions (∼50% to near-100% RH), where viability decreases with decreasing RH in medium containing salts only. In this regime, evaporation is intense, and salts are concentrated enough to be toxic. The solution can even become supersaturated. The toxic effect of salts is supported by the finding that NaCl at concentrations in excess of 1 M (i.e., five times physiological levels and easily achieved in an aerosol following evaporation [39]) leads to significant changes to membrane structure and elasticity (38). (iii) The third involves dry conditions (<∼50% RH), where salts crystallize and viability is maintained. When the RH is less than the ERH, salts crystallize, and thus, their toxic effects are eliminated.

By the same mechanism, acidification outside the host cell without the presence of the target membrane may induce conformational changes in the glycoproteins that, if irreversible, would inactivate the virus’s fusion activity and, hence, infectivity (17, 30, 56). In contrast, pretreatment at low pH of a virus that does not require acid-catalyzed conformational changes preceding fusion generally does not compromise its infectivity (17, 30). In particular, proteins have repeatedly been shown to be protective for various enveloped viruses (1, 51, 54). Their buffering effects may explain, in part, this observation. Nevertheless, this analysis indicates that the change in pH associated with droplet evaporation at a specific RH may be a potential mediator of virus viability.

The relationship between aerosolized viruses and RH is probably a combined function of properties of the virus and the interactions among the virus, solutes, and water molecules. RH may affect the viability of a virus in aerosols by controlling the amount of water retained, the equilibrium size of an aerosol and, thus, its surface area, the concentrations of solutes, and its pH.