Project Description

TP12: Role of the host stress response in the establishment of viral persistence: comparative analysis of HCV and HAV infection

Host stress responses regulate multiple pathways including inflammatory and immune responses, thereby likely influencing the fate of a viral infection. In this first funding period, we will (i) develop a quiescent cell culture model that allows studying the dynamics of the stress response to chronic virus infections such as hepatitis C virus (HCV) in a physiological context closer to hepatocytes in the liver, and (ii) generate a time-resolved map of transcriptional and translational reprogramming that occur in persistent HCV infection. Using an acute hepatitis A virus (HAV) infection as model of a non-persistent virus, we aim at identifying key differences to HCV that influence the establishment of a persistent infection.
Roth H, Magg V, Uch F, Mutz P, Klein P, Haneke K, Lohmann V, Bartenschlager R, Fackler OT, Locker N, Stoecklin G, Ruggieri A. 2017. Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses. MBio. 8(1). pii: e02150-16. doi: 10.1128/mBio.02150-16. Erratum in: MBio. 2017 Apr 18;8(2)
Grünvogel O, Esser-Nobis K, Reustle A, Schult P, Müller B, Metz P, Trippler M, Windisch MP, Frese M, Binder M, Fackler O, Bartenschlager R, Ruggieri A, Lohmann V. 2015. Dead box helicase 60-like (DDX60L) is an interferon stimulated gene restricting hepatitis C virus replication in cell culture. J Virol 89:10548-68
Hiet M-S, Bauhofer O, Zayas M, Roth H, Tanaka Y, Eberle F, Schirmacher P, Willemsen J, Binder M, Lohmann V, Lotteau V, Ruggieri A*, Bartenschlager R*. 2015. Control of temporal activation of hepatitis C virus-induced interferon response by domain 2 of nonstructural protein 5A. J Hepatol 63:829-37. *co- corresponding authors.
Ruggieri A, Dazert E, Metz P, Hofmann S, Bergeest JP, Mazur J, Bankhead P, Hiet MS, Kallis S, Alvisi G, Samuel CE, Lohmann V, Kaderali L, Rohr K, Frese M, Stoecklin G, Bartenschlager R. 2012. Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection. Cell Host Microbe 12: 71-85.
Bauhofer O, Ruggieri A, Schmid B, Schirmacher P, Bartenschlager R. 2012. Persistence of HCV in qui- escent hepatic cells under conditions of an interferon-induced antiviral response. Gastroenterology 143: 429-438.
Metz P, Dazert E, Ruggieri A, Mazur J, Kaderali L, Kaul A, Zeuge U, Trippler M, Lohmann V, Binder M, Frese M, Bartenschlager R. 2012. Identification of type I and type II interferon-induced effectors controlling hepatitis C virus replication. Hepatology. 56:2082-93.