Various influenza A viruses (AIVs) have infected humans in the last decade. These infections result from spill over into humans at times of AIV poultry outbreaks with severe clinical consequences for those infected. These AIVs do not have the ability to be efficiently spread among humans via respiratory droplets or aerosols and subsequently cause a pandemic. However, adaptation of these avian influenza viruses to humans by mutation or reassortment may change this. We know that AIVs require adaptation of several critical characteristics in order to effectively spread between humans. Therefore, in order for human pandemic emergence, AIV that crosses into a human host must already be sufficiently able, or must rapidly adapt to overcome these constraints to transmit to a subsequent human host before infection is cleared by an immune response. In this study, we used mice and analysed the mutations acquired by avian origin H7N9 and H9N2 isolates in a temporal fashion during a single infection cycle in individual hosts. Viruses recovered from infected mice lungs were subjected to Next Generation sequencing (NGS) to identify mammalian adaptation enhancing mutations. Moreover, the timing of these mutations was correlated to the host response, with particular emphasis on cytokine profile and innate immune responses during the time prior to and following viral sequence changes to help understand the virus-host dynamics and the host environment favouring adaptation. Furthermore, understanding of the determinants and mechanisms of adaptation and transmission may aid in assessing the risks posed by avian influenza A viruses to human health.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article metrics loading...

Loading full text...

Full text loading...


Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error