Reference record
Tropism and Pathogenesis of Influenza Virus and Coronavirus in Human Brain Explant Culture
NCT05375006
First Published (first received 2022 May 16)https://clinicaltrials.gov/show/NCT05375006 (https://clinicaltrials.gov/show/NCT05375006)
Trial registry recordNo Results
Background:
Influenza and coronavirus have been repeatedly causing pandemic recently. Like the Influenza
A/H7N9 virus has caused five epidemics in China since its first detection in East China in
2013. In 2017, the previously low pathogenic avian influenza (LPAI) H7N9 virus underwent
mutation in its haemagglutinin to give to a highly pathogenic avian influenza (HPAI) virus
causing 32 human cases and potentially poses a threat to animal and human health. More
recently, the SARS-CoV-2 pandemic has been heavily affecting the world. Therefore an
effective risk assessment platform is urgently required for better pandemic preparation.
Hypothesis:
The tissue tropism and pathogenesis of a newly emerged infectious viruses, like the
highlypathogenic influenza, like H7N9 and coronavirus, like SARS-CoV-2 would be different
from that of their low pathogenic subtype and it would infect and replicate the human
respiratory system more efficiently.
Because of its resistance to oseltamivir for influenza and no effective antiviral for
coronavirus, investigators therefore propose to set up an novel and effective risk assessment
platform for emerging infectious viruses.
Experimental Design:
The tissue tropism and viral replication kinetics of a HPAI and LP influenza and coronavirus
will be determined in ex vivo cultures of human brain and compared with their LP subtype. The
replication competence and innate immune responses of influenza and coronavirus will be
studied and compared with other LP virus in in vitro cultures of human brain cells and human
microvascular endothelial cells (HMVEC) both isolated from human brain tissues.
Expected outcomes:
HPAI influenza and coronavirus particularly SARS-CoV-2 will infect and replicate the human
brain tissues and cells more efficiently than their LP subtype. Besides, HPAI influenza and
SARS-CoV-2 will induce dysregulated host innate immune response than the LP subtype