PROJECT SUMMARY
Influenza A viruses (IAV) significantly burden society by causing millions of illnesses annually and generating
significant economic losses. Transmission of IAV between humans is thought to occur via virus-laden droplets
generated by infected individuals as they cough, sneeze, talk and breathe. IAV access the respiratory mucosa
of a new host by being delivered through direct contact, self-inoculation after touching surfaces containing viable
virus or through airborne transmission. The outcome of airborne transmission is dictated by the size of the
aerosols, which determines the duration for which they are suspended in air, how far they travel, and their site
of deposition in the respiratory tract. While direct, indirect, and airborne transmission are considered to contribute
to IAV spreading, their individual relevance is unclear. Moreover, whether the contribution of different mode(s)
of exposure changes with context, such as host immunity or environmental conditions, remains unknown. We
hypothesize that, in a recipient host, the efficiency of infection is modulated by the mode and
circumstances of exposure, which are defined by the site of viral deposition and effects of the
environment on host responses. To address this hypothesis, we will focus on the recipient host as this aspect
of transmission can be tightly manipulated experimentally. We will perform intranasal and aerosol inoculations
to model direct and airborne modes of infection in guinea pigs. To monitor the efficiency of infection, I will use
barcoded libraries of influenza A/California/07/2009 (H1N1pdm09) and A/Panama/2007/99 (H3N2) viruses to
assess the number of unique viruses establishing infection. We predict that the viral barcodes will provide a
sensitive method for evaluating the intensity of exposure. Additionally, I will test varying ambient temperature
and relative humidity levels to assess the impact of environmental conditions on modes of exposure to IAV and
host immune responses. In Aim 1, I will examine the relationship between the intensity of exposure and
established barcode diversity given distinct modes of exposure. In Aim 2, I will assess the extent to which
environmental conditions impact host immune responses and the efficiency of IAV infection by different modes.
The impact of this research is to advance knowledge of external factors defining host susceptibility and IAV
infection and transmission potential. Our results will deepen understanding of the roles of different modes of
exposure in leading to infection and thereby enable development of effective interventions to limit IAV spread.