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Ultra-low dose aerosol infection provides an improved murine model of tuberculosis

ABSTRACT: Ultra-low dose aerosol infection provides an improved murine model of tuberculosis

PROVIDER: PRJNA666628 | ENA |

REPOSITORIES: ENA

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Project description:Multiple respiratory viruses including Influenza A virus (IAV) can be transmitted via expiratory aerosol particles, and many studies have established that environmental conditions can affect viral infectivity during airborne transmission. Low aerosol pH was recently identified as a major factor influencing the infectivity of aerosol-borne IAV and SARS-CoV-2, however, there is a fundamental lack of understanding as to the mechanisms leading to viral inactivation within the acidic aerosol micro-environment. Here, we identified that the early stages of the IAV infection cycle were impacted by transient exposure to acidic aerosol conditions (pH below 5.5), which was primarily attributed to loss of binding function of the viral protein haemagglutinin. Viral capsid integrity was also somewhat affected by transient acidic exposure. We then characterised the structural changes associated with loss of viral infectivity using whole-virus hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and observed discrete regions of unfolding in the external viral protein haemagglutinin and in the internal matrix protein 1. Viral nucleoprotein structure appeared to be unaffected by exposure to acidic aerosol conditions, and no changes to viral genome integrity or to lipids within the viral envelope were detected using our whole-virus methods. Collectively, these data indicate that viral inactivation observed under indoor aerosol conditions is mediated by specific protein conformational changes, particularly to haemagglutinin. This study additionally provides a proof-of-concept that HDX-MS is a highly effective method for characterisation of internal and external proteins of whole enveloped viruses such as IAV. Overall, improved understanding of the fate of respiratory viruses within exhaled aerosols will aid the development of novel strategies and therapeutics to control the severity of seasonal and/or pandemic influenza, and constitutes a global public health priority.

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Ultra-low dose aerosol infection provides an improved murine model of tuberculosis

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