Project Details
Projekt
Role of importin-alpha isoforms in MERS-Coronavirus interspecies transmission and subsequent infection of the human respiratory tract
Applicant
Professorin Dr. Gülsah Gabriel
Subject Area
Virology
Term
from 2016 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 288266605
The aim of this research proposal is to study the role of importin-alpha isoforms in defining species barriers of coronaviruses with a special emphasis on MERS-CoV infections in the respiratory tract. Therefore, we would like to first sequence and analyze the diversity of importin-alpha isoforms derived from bats and camels as original reservoir hosts in comparison to those of humans. Next, we would like to identify coronavirus proteins originating from animals as well as humans that interact with importin-alpha isoforms in cells of different species. Then, we will analyze viral replication kinetics of recombinant coronaviruses that either contain the animal or the human importin-alpha interacting viral gene in primary animal and human importin-alpha knockdown airway epithelial cells. The virus replication in these cells will then be correlated with the induction of proinflammatory cytokine responses. Herein, we will particularly analyze whether differential importin-alpha binding and replication correlates with differences in the nuclear transport of key transcription factors, such as STAT1 and NF-kappaB. Finally, we will perform an unbiased transcriptome analysis in these coronavirus infected primary airway epithelial cells to elucidate underlying mechanisms in potential evasion of host innate immune responses in a species dependent manner. These studies will allow us to understand the molecular basis on how coronaviruses might circumvent innate immune responses in a host dependent fashion that might as a consequence facilitate cross species transmission of emerging viruses of zoonotic origin from animal-to-man as well as promote respiratory infection in humans.
DFG Programme
Priority Programmes
Co-Investigator
Dr. Stephanie Bertram
