Project description:The 2022 North American outbreak of 2.3.4.4b H5N1 avian influenza virus revealed significant mammalian adaptation and pathogenicity, yet mechanisms remain unclear. To address this knowledge gap, we investigated the North American H5N1 strain (GA/W22-145E/22), which demonstrated unique immune cell-mediated systemic dissemination, neuroinvasion, and 100% mortality in ferrets, unlike the non-lethal Eurasian strain (KR/W811/21). Genomic and reverse genetics studies identified PB2478I and NP450N mutations as key determinants of enhanced polymerase activity, immune cell tropism, and pathogenicity. Mutant GA/W22-145E/22 virus carrying PB2478V/NP450S showed complete survival without systemic dissemination. Furthermore, GA/W22-145E/22 demonstrated robust replication in human PBMCs and bovine mammary gland organoids, raising concerns about zoonotic spillover. These findings underscore PB2478I and NP450N as pivotal markers of pathogenicity, emphasizing the urgent need for enhanced surveillance and targeted interventions
Project description:National Surveillance Plan for Influenza A Virus (IAV) in Swine - Influenza A virus (IAV) sequences from domestic swine in the U.S.
Project description:In recent years, the roles of microRNAs playing in the regulation of influenza viruses replication caused researchers' much attenion. However, much work focused on the interactions between human, mice or chicken microRNAs with human or avian influenza viruses rather than the interactions of swine microRNAs and swine influenza viruses. To investigate the roles of swine microRNAs playing in the regulation of swine influenza A virus replication, the microRNA microarray was performed to identify which swine microRNAs were involved in swine H1N1/2009 influenza A virus infection.
