Primary bovine embryonic fibroblasts demonstrate variable fitness following infection with highly pathogenic avian influenza H5N1 strains and are susceptible to a recently circulating human 2009 pandemic lineage H1N1 strain

Zoonotic spillover to humans with avian influenza A subtypes, such as H5N1, can have extraordinarily high mortality rates. Recently, highly pathogenic avian influenza (HPAI) H5N1 has spread to dairy cattle and caused widespread disease in over a thousand herds across the United States. This widespread infection not only poses notable economic challenges to agricultural industries but also represents a notable concern to human public health. While studies of infection dynamics of HPAI H5N1 in cattle remain crucial, animal handling restrictions and a lack of well-characterized cell culture models make this work challenging. The significance of our research lies in identifying an <i>in vitro</i> system-primary bovine embryonic fibroblasts (BeEFs)-as a physiologically relevant <i>in vitro</i> system for studying these infection dynamics, helping to mitigate the limitations imposed by stringent animal handling requirements.