Carol M. Sheppard

May 14, 2024 | nature.com | Ecco Staller |Loïc Carrique |Haitian Fan |Jeremy Keown |Carol M. Sheppard |Wendy Barclay | +1 more

AbstractAvian influenza A viruses (IAVs) pose a public health threat, as they are capable of triggering pandemics by crossing species barriers. Replication of avian IAVs in mammalian cells is hindered by species-specific variation in acidic nuclear phosphoprotein 32 (ANP32) proteins, which are essential for viral RNA genome replication. Adaptive mutations enable the IAV RNA polymerase (FluPolA) to surmount this barrier.

Oct 10, 2023 | nature.com | Daniel H. Goldhill |Carol M. Sheppard |Ksenia Sukhova |Jonathan Brown |Ciara Y. Campbell |Salik Nazki | +6 more

AbstractChickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, influenza A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 to generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction. After IAV challenge, 9/10 edited chickens remain uninfected. Challenge with a higher dose, however, led to breakthrough infections.

Oct 10, 2023 | nature.com | Carol M. Sheppard |Daniel H. Goldhill |Olivia Platt |Ksenia Sukhova |Thomas Peacock |Ervin Fodor

AbstractHuman ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth.