Relative humidity differentially modulates decay of structurally distinct respiratory viruses in deposited human saliva particles

Respiratory viruses pose a major threat to human health. Environmental virus persistence in respiratory secretions is essential for successful spread, yet studies have focused largely on a select few viruses in non-physiological matrices. Here, we compared the stability of structurally distinct human respiratory viruses, adenovirus, influenza virus, and rhinovirus, in deposited particles of pooled human saliva under indoor-relevant relative humidity (RH) conditions. Adenovirus exhibited <2.2-log10 decay over 6 h regardless of RH, while rhinovirus exhibited significantly greater degradation (>3.8-log10, at 50% and 80% RH). Influenza virus showed minimal decay at 20% and 50% RH but degraded significantly more (3-log10) at 80% RH. To distinguish aspects of human saliva that are key determinants in driving virus decay, we recapitulated saliva composition using the inorganic solute and protein concentrations determined via ion-coupled plasma mass spectrometry and proteomics, respectively. Rhinovirus was significantly more stable in simulated saliva than in human saliva at 50% RH, while influenza virus and adenovirus behaved similarly in both matrices. These findings emphasize virus-specific environmental persistence and highlight limitations of relying on a single virus and particle matrix for defining public health strategies. Ultimately, these insights will contribute to approaches for mitigating environmental transmission of distinct respiratory pathogens.