Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
Mark Dittmar
Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Michael J Mallory
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
Prasanna Bhat
Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States
Max B Ferretti
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States; Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Beatriz MA Fontoura
Department of Cell Biology, UT Southwestern Medical Center, Dallas, United States
Sara Cherry
Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States; Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here, we show that infection of human lung epithelial cells with influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. Although these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein required for efficient splicing of the IAV M transcript in nuclear speckles. Finally, we find an increase in hnRNP K in nuclear speckles upon IAV infection, which may alter accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication.
