Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets
Copyright: © 2023 Siegers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
---|---|
Enthalten in: |
PLoS pathogens - 19(2023), 3 vom: 28. März, Seite e1011214 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Siegers, Jurre Y [VerfasserIn] |
---|
Links: |
---|
Themen: |
Journal Article |
---|
Anmerkungen: |
Date Completed 24.03.2023 Date Revised 09.04.2023 published: Electronic-eCollection Citation Status MEDLINE |
---|
doi: |
10.1371/journal.ppat.1011214 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM354036009 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM354036009 | ||
003 | DE-627 | ||
005 | 20231226061345.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1371/journal.ppat.1011214 |2 doi | |
028 | 5 | 2 | |a pubmed24n1180.xml |
035 | |a (DE-627)NLM354036009 | ||
035 | |a (NLM)36897923 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Siegers, Jurre Y |e verfasserin |4 aut | |
245 | 1 | 0 | |a Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 24.03.2023 | ||
500 | |a Date Revised 09.04.2023 | ||
500 | |a published: Electronic-eCollection | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright: © 2023 Siegers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
700 | 1 | |a Ferreri, Lucas |e verfasserin |4 aut | |
700 | 1 | |a Eggink, Dirk |e verfasserin |4 aut | |
700 | 1 | |a Veldhuis Kroeze, Edwin J B |e verfasserin |4 aut | |
700 | 1 | |a Te Velthuis, Aartjan J W |e verfasserin |4 aut | |
700 | 1 | |a van de Bildt, Marco |e verfasserin |4 aut | |
700 | 1 | |a Leijten, Lonneke |e verfasserin |4 aut | |
700 | 1 | |a van Run, Peter |e verfasserin |4 aut | |
700 | 1 | |a de Meulder, Dennis |e verfasserin |4 aut | |
700 | 1 | |a Bestebroer, Theo |e verfasserin |4 aut | |
700 | 1 | |a Richard, Mathilde |e verfasserin |4 aut | |
700 | 1 | |a Kuiken, Thijs |e verfasserin |4 aut | |
700 | 1 | |a Lowen, Anice C |e verfasserin |4 aut | |
700 | 1 | |a Herfst, Sander |e verfasserin |4 aut | |
700 | 1 | |a van Riel, Debby |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t PLoS pathogens |d 2005 |g 19(2023), 3 vom: 28. März, Seite e1011214 |w (DE-627)NLM158124782 |x 1553-7374 |7 nnns |
773 | 1 | 8 | |g volume:19 |g year:2023 |g number:3 |g day:28 |g month:03 |g pages:e1011214 |
856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.ppat.1011214 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 19 |j 2023 |e 3 |b 28 |c 03 |h e1011214 |