In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 3 ( 2023-3-10), p. e1011214-
Kurzfassung:
Central nervous system (CNS) disease is the most common extra-respiratory tract complication of influenza A virus infections in humans. Remarkably, zoonotic highly pathogenic avian influenza (HPAI) H5N1 virus infections are more often associated with CNS disease than infections with seasonal influenza viruses. Evolution of avian influenza viruses has been extensively studied in the context of respiratory infections, but evolutionary processes in CNS infections remain poorly understood. We have previously observed that the ability of HPAI A/Indonesia/5/2005 (H5N1) virus to replicate in and spread throughout the CNS varies widely between individual ferrets. Based on these observations, we sought to understand the impact of entrance into and replication within the CNS on the evolutionary dynamics of virus populations. First, we identified and characterized three substitutions–PB1 E177G and A652T and NP I119M - detected in the CNS of a ferret infected with influenza A/Indonesia/5/2005 (H5N1) virus that developed a severe meningo-encephalitis. We found that some of these substitutions, individually or collectively, resulted in increased polymerase activity in vitro. Nevertheless, in vivo, the virus bearing the CNS-associated mutations retained its capacity to infect the CNS but showed reduced dispersion to other anatomical sites. Analyses of viral diversity in the nasal turbinate and olfactory bulb revealed the lack of a genetic bottleneck acting on virus populations accessing the CNS via this route. Furthermore, virus populations bearing the CNS-associated mutations showed signs of positive selection in the brainstem. These features of dispersion to the CNS are consistent with the action of selective processes, underlining the potential for H5N1 viruses to adapt to the CNS.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011214
DOI:
10.1371/journal.ppat.1011214.g001
DOI:
10.1371/journal.ppat.1011214.g002
DOI:
10.1371/journal.ppat.1011214.g003
DOI:
10.1371/journal.ppat.1011214.g004
DOI:
10.1371/journal.ppat.1011214.g005
DOI:
10.1371/journal.ppat.1011214.g006
DOI:
10.1371/journal.ppat.1011214.g007
DOI:
10.1371/journal.ppat.1011214.t001
DOI:
10.1371/journal.ppat.1011214.t002
DOI:
10.1371/journal.ppat.1011214.t003
DOI:
10.1371/journal.ppat.1011214.t004
DOI:
10.1371/journal.ppat.1011214.t005
DOI:
10.1371/journal.ppat.1011214.s001
DOI:
10.1371/journal.ppat.1011214.s002
DOI:
10.1371/journal.ppat.1011214.s003
DOI:
10.1371/journal.ppat.1011214.s004
DOI:
10.1371/journal.ppat.1011214.s005
DOI:
10.1371/journal.ppat.1011214.s006
DOI:
10.1371/journal.ppat.1011214.s007
DOI:
10.1371/journal.ppat.1011214.s008
DOI:
10.1371/journal.ppat.1011214.s009
DOI:
10.1371/journal.ppat.1011214.s010
DOI:
10.1371/journal.ppat.1011214.s011
DOI:
10.1371/journal.ppat.1011214.s012
DOI:
10.1371/journal.ppat.1011214.s013
DOI:
10.1371/journal.ppat.1011214.s014
DOI:
10.1371/journal.ppat.1011214.s015
DOI:
10.1371/journal.ppat.1011214.s016
DOI:
10.1371/journal.ppat.1011214.r001
DOI:
10.1371/journal.ppat.1011214.r002
DOI:
10.1371/journal.ppat.1011214.r003
DOI:
10.1371/journal.ppat.1011214.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2205412-1
