Behaviour of Highly Pathogenic Avian Influenza (H5N1) in Cattle and Impact of Virus Gene Signatures on Disease and Potential Transmission to Humans

Highly pathogenic avian Influenza (HPAI) H5N1 virus usually infects avian species. However, in March 2024, HPAI (H5N1) was detected for the first time in Texas dairy cattle subsequently spreading to several herds through the USA. The infected cows showed flu-like symptoms, including fever, reduced feed intake, thick, discolored milk associated with decreased milk production. This unprecedented spillover event in cattle underscores the capacity of HPAI H5N1 to expand into a new host, raising a series of questions, including: What routes of exposure lead to infection and how does this alter the trajectory of clinical disease? To what extent does the viral gene pattern become a determinant of disease outcome? What is the potential risk that HPAI H5N1 spill back to the environment to infect birds, wildlife, and human? This proposal will address these critical questions through two specific aims: Aim 1. To determine which routes of administration in dairy cows establish infection and the viral shedding associated with them to assess the risk of potential airborne transmission to humans. Aim 2. To characterize which virological gene signatures can establish infection and disease in cows, and how the genomic composition will impact the shedding of the virus to the environment posing risk of airborne transmission to human. Our study provides a strong One Health approach to study the impact of HPAI H5N1 viruses at the interface of human, animal and environmental system. We will generate evidence-based data rapidly and disseminate to relevant knowledge users in public health, agricultural sectors including the dairy industry, wildlife health and conservation, and veterinary epidemiology. Our research will enhance Canada's response and preparedness efforts to the ongoing HPAI outbreak.