Project Description

TP16: Unravelling the role of DNA repair in the formation of the hepatitis B virus cccDNA persistence reservoir

HBV persistence is enabled by a highly stable nuclear form of the viral genome, termed cccDNA, which is formed from the relaxed circular DNA genome in infectious virions. This multistep conversion requires as yet poorly understood cellular DNA repair activities. One aim of this project is to unravel the mechanistic role in cccDNA formation of specific candidate DNA repair factors. The other is to characterize the completely unexplored general impact of HBV on the cell´s DNA damage response and vice versa, including activation vs. suppression of innate immune responses.
Wing PA, Davenne T, Wettengel J, Lai AG, Zhuang X, Chakraborty A, D'Arienzo V, Kramer C, Ko C, Harris JM, Schreiner S, Higgs M, Roessler S, Parish JL, Protzer U, Balfe P, Rehwinkel J, McKeating JA. 2019. A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis. Life Sci Alliance. 2(2). pii: e201900355. doi: 10.26508/lsa.201900355.
Schuch A, Salimi Alizei E, Heim K, Wieland D, Kiraithe MM, Kemming J, Llewellyn-Lacey S, Sogukpinar Ö, Ni Y, Urban S, Zimmermann P, Nassal M, Emmerich F, Price DA, Bengsch B, Luxenburger H, Neumann-Haefelin C, Hofmann M, Thimme R. 2019. Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load. Gut. 2019 Jan 8. pii: gutjnl-2018-316641. doi: 10.1136/gutjnl-2018-316641. (Epub ahead of print)
Nassal M. 2018. Chronic hepatitis B: divide and conquer? Gut. 67(3):400-402. doi: 10.1136/gutjnl-2017-314255.
Müncheberg S, Hay TR, Ip HW., Meyer T, Weiß C, Brenke J, Masser S, Hadian K, Dobner T, Schreiner S. 2018. E1B-55K mediated regulation of RNF4 STUbL promotes HAdV gene expression. J Virol. 92(13).pii: e00164-18. doi: 10.1128/JVI.00164-18.
Freudenberger N., Hay R. T., Groitl P., Dobner T., Schreiner S, 2018. HAdV pV core protein is targeted by the host SUMOylation machinery to pursue essential viral functions. J Virol. 92(4). pii: e01451-17. doi: 10.1128/JVI.01451-17
Inturi R., Mun K., Singethan K., Schreiner S, Punga T. 2018. Human Adenovirus Infection Counteracts Antiviral Activity of the celllar MKRN1 E3 Ubiquitin Ligase. J Virol. 17;92(3). pii: e01154-17. doi: 10.1128/JVI.01154-17
Schreiner S, Nassal M. 2017. A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation-and Beyond? Viruses. 9(5). pii: E125. doi: 10.3390/v9050125. Review.
Nassal M. 2015. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut 64:1972-1984. Review summarizing cccDNA state-of-the-art 2015
Hoh A, Heeg M, Ni Y, Schuch A, Binder B, Hennecke N, Blum, HE, Nassal M, Protzer U, Hofmann M, Urban S, Thimme R. 2015. HBV-infected HepG2 hNTCP cells serve as a novel immunological tool to an- alyse the antiviral efficacy of CD8+ T cells in vitro. J Virol 89:7433-8
Wimmer P, Schreiner S. 2015. Viral Mimicry to usurp Ubiquitin and SUMO host pathways. Review. Viruses 7: 4854-77
Wimmer P, Berscheminski J, Blanchette P, Groitl P, Branton PE, Hay RT, Dobner T, Schreiner S. 2015. PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation by functionally inhibiting the tumor suppressor p53. Oncogene; epub doi: 10.1038/onc.2015.63.
Königer C, Wingert I, Marsmann M, Rösler, C, Beck J, Nassal M. 2014. Involvement of the host DNA- repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. Proc Natl Acad Sci USA 111:E4244-53
Berscheminski J, Wimmer P, Brun J, Ip WH, Groitl P, Horlacher T, Jaffray E, Hay RT, Dobner T, Schrei- ner S. 2014. Sp100 isoform-specific regulation of human adenovirus 5 gene expression, J Virol 88: 6076- 92
Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Falth M, Stindt J, Königer C, Nassal M, Kubitz R, Sultmann H, Urban S. 2014. Hepatitis B and D viruses exploit sodium taurocholate co-transporting poly- peptide for species-specific entry into hepatocytes. Gastroenterology 146:1070-83
Schreiner S, Kinkley S, Bürck C, Mund A, Wimmer P, Schubert T, Groitl P, Will H, Dobner T. 2013. SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection. PLoS Pathog 9:e1003775
Schreiner S, Wimmer P, Dobner T. 2012. Adenovirus degradation of cellular proteins. Future Microbiol 7:211-225. Review.
Köck J, Rösler C, Zhang JJ, Blum HE, Nassal M*, Thoma C*. 2010. Generation of covalently closed cir- cular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog 6:e1001082. *shared senior authorship