Prepared for viral amplification – how two flaviviral host factors preprocess the viral RNA genome to modulate its replication — ASN Events
  1. Schedule
  2. Session 5: Poster Session A
  3. Prepared for viral amplification – how two flaviviral host factors preprocess the viral RNA genome to modulate its replication

Prepared for viral amplification – how two flaviviral host factors preprocess the viral RNA genome to modulate its replication (#185)

Tobias Schmidt 1 , Susann Friedrich* 1 , Paul Knick 2 , René Geissler 3 , Hauke Lilie 1 , Ralph P. Golbik 1 , Sven-Erik Behrens 1
  1. MLU Halle-Wittenberg, Halle/Saale, Germany
  2. Scil Proteins, Halle, Germany
  3. Molecular Biology and Genetics, Cornell University, Ithaca, USA

* equal contribution

A crucial aspect of current virology of positive-strand RNA viruses (family Flaviviridae) is to define the function of cellular factors supporting the viral genome amplification during their life cycle. Often, these factors ultimately determine the natural host of the respective virus and are generally called host factors. Some previous work aimed at identifying host factors interacting with the viral polymerases or genomic RNA. In most cases the molecular mechanisms how host factors modulate the viral genome amplification remain unknown1. This study focused on characterizing cellular host factors that assist genomic RNA replication of the important flaviviral human pathogens West Nile Virus (WNV) and Hepatitis C Virus (HCV). Recently, we identified the p45 isoform of the RNA-binding protein AUF12 and, previously, the dsRNA-binding protein complex NF90-NF45 as important host factors of WNV and HCV replication, respectively3. We here demonstrate that the both identified proteins share an RNA chaperone activity, which aids structural rearrangement of the genomic RNA. Based on special structural constraints of the viral RNA substrates, the two proteins fundamentally differ in the realization of the chaperoning effect. In particular, the RNA chaperone activity involves some stabilizing or destabilizing effects that depend on specific properties of the RNA substrate. In performing a comparative biophysical-mechanistic analysis of the recombinant proteins concerning structural properties and functional aspects, we provide a model in which manner these host factors express their RNA chaperone activity. Structural RNA elements are rearranged to preprocess the respective viral genome and to modulate the viral replication process.

  1. Ahlquist P, Noueiry AO, Lee WM, Kushner DB, Dye BT. (2003) Host factors in positive-strand RNA virus genome replication. J. Virol. 77:8181–8186
  2. Friedrich et al., submitted
  3. Isken O, Baroth M, Grassmann CW, Weinlich S, Ostareck DH, Ostareck-Lederer A, Behrens S-E, (2007) Nuclear factors are involved in hepatitis C virus RNA replication. RNA 13:1675–1692