Role of Microbiome Diversity, Microbial Transcriptome and Host Gene Expression in the Respiratory Track of Humans in Influenza Virus Infection
Infection susceptibility and disease severity is regulated by a complex balance between the genotype of the pathogen, the genotype of the host, and environmental factors. While many studies are being conducted to evaluate the contribution of these three factors in many infectious diseases, another variable that until recently has been overlooked is the metagenome (or microbial community including viruses, bacteria and microeukaryotes which inhabit the human body). Many viruses, including influenza virus, infect through mucosal surfaces that are colonized with resident microorganisms. Years of co-evolution of a virus with its host and its metagenome have likely selected for viruses that are able to infect a host in the presence of the most prevalent metagenome, so the characteristics of the metagenome are likely to make an impact in infection susceptibility and disease outcome. Moreover, the host innate and adaptive immune factors elicited in response to viral infection are likely to make a big impact in the normal (basal) flora, which may influence the susceptibility to pathogenic bacteria colonization. We are specifically interested in: i) the effect of seasonality in the diversity and expression profile of the metagenome, ii) the role of the respiratory tract metagenome in promoting or inhibiting infection by influenza viruses, and iii) how changes in the metagenome after viral infection may promote secondary bacterial colonization and enhance disease. Currently we still lack fundamental studies that address how variable the metagenome at the URT is among humans, how this metagenome affects susceptibility to respiratory virus infection and how the metagenome responds to virus infection in the general population.
White Paper Access
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This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract numbers N01-AI30071 and/or HHSN272200900007C.