Project Details
Projekt
Molecular mechanisms of Zika virus-associated neuropathogenesis and possible link to virus evolution
Subject Area
Virology
Term
from 2018 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 391587080
Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family, which includes other globally relevant arthropod-transmitted human pathogens such as dengue virus and yellow fever virus. Although the majority of ZIKV infections are asymptomatic, ZIKV has received increasing public awareness because of its recent pandemic spread and its recognition as an important human pathogen causing severe neurological complications, most notably microcephaly. While the neurotropism of ZIKV is becoming increasingly clear, the molecular mechanisms underlying this pathogenesis are largely unknown. We have recently found that infection of human neural progenitor cells with ZIKV triggers profound cytoskeletal rearrangements. Moreover, we and others found that pathogenic ZIKV strains appear to have acquired distinct mutations that might contribute to pathologies. Based on these findings in this proposal we will examine the mechanisms underlying ZIKV infection-induced cell damage as well as the role of ZIKV evolution for this process. In close collaboration between the Bartenschlager laboratory in Heidelberg and the Long laboratory in Shanghai we will employ in vitro and in vivo models to study two complementary and inter-related approaches. The first one addresses the mechanism of ZIKV-induced alterations of the cytoskeleton and the consequences for neuronal cells and their development. The second approach takes advantage of a newly developed ZIKV infectious clone and aims to determine whether ZIKV mutations identified in patients with severe infections play a role in ZIKV fitness and neuro-pathogenesis and how these mutations might impact on cytoskeleton alterations of neuronal cells. In this way we aim to map and characterize the viral determinants responsible for cytoskeleton-dependent and -independent neuropathogenesis.
DFG Programme
Research Grants
International Connection
China
Partner Organisation
National Natural Science Foundation of China
Cooperation Partner
Professor Dr. Gang Long
