Mary Wilson
Well-known member
Published28 June 2023
DOI https://doi.org/10.1038/s41586-023-06261-8
Pinto, R.M., Bakshi, S., Lytras, S. et al.
Abstract
Spillover events of avian influenza A viruses (IAVs) to humans could represent the first step in a future pandemic[SUP]1[/SUP]. Several factors that limit the transmission and replication of avian IAVs in mammals have been identified. There are several gaps in our understanding to predict which virus lineages are more likely to cross the species barrier and cause disease in humans[SUP]1[/SUP]. Here, we identified human BTN3A3 (butyrophilin subfamily 3 member A3)[SUP]2[/SUP] as a potent inhibitor of avian IAVs but not human IAVs. We determined that BTN3A3 is expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts primarily at the early stages of the virus life cycle by inhibiting avian IAV RNA replication. We identified residue 313 in the viral nucleoprotein (NP) as the genetic determinant of BTN3A3 sensitivity (313F or, rarely, 313L in avian viruses) or evasion (313Y or 313V in human viruses). However, avian IAV serotypes, such as H7 and H9, that spilled over into humans also evade BTN3A3 restriction. In these cases, BTN3A3 evasion is due to substitutions (N, H or Q) in NP residue 52 that is adjacent to residue 313 in the NP structure[SUP]3[/SUP]. Thus, sensitivity or resistance to BTN3A3 is another factor to consider in the risk assessment of the zoonotic potential of avian influenza viruses.
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https://www.nature.com/articles/s41586-023-06261-8#citeas
__________________________________________________ ____________
A preview of this full-text is provided by Springer Nature. ResearchGate
Content available from Nature
... Abstract and Figures
Inluenza A viruses (IAVs) cause a substantial global health burden
and circulate both in humans and animal species, including domestic
poultry, pigs, dogs and horses. Wild aquatic birds are the main natu-
ral reservoir of IAVs4. Ducks, shorebirds, gulls and other waterbirds
harbour 16 haemagglutinin and 9 neuraminidase subtypes5. IAVs
from wild bird reservoirs can infect economically important birds,
such as chickens, turkeys, quail and other gallinaceous species and
domestic waterfowl 4. The population density of domestic birds and
the direct exposure to infected birds facilitates avian IAV spillovers
into susceptible mammals, including humans. Avian IAVs can also
further reassort (that is, exchange genome segments) with viruses
established in susceptible species resulting in the rich IAV genetic
diversity. In humans, the influenza pandemics of 1918, 1957, 1968 and
2009 were all caused by viruses containing genomic segments of
avian origin. ...
https://www.researchgate.net/public...the_zoonotic_potential_of_influenza_A_viruses
DOI https://doi.org/10.1038/s41586-023-06261-8
Pinto, R.M., Bakshi, S., Lytras, S. et al.
Abstract
Spillover events of avian influenza A viruses (IAVs) to humans could represent the first step in a future pandemic[SUP]1[/SUP]. Several factors that limit the transmission and replication of avian IAVs in mammals have been identified. There are several gaps in our understanding to predict which virus lineages are more likely to cross the species barrier and cause disease in humans[SUP]1[/SUP]. Here, we identified human BTN3A3 (butyrophilin subfamily 3 member A3)[SUP]2[/SUP] as a potent inhibitor of avian IAVs but not human IAVs. We determined that BTN3A3 is expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts primarily at the early stages of the virus life cycle by inhibiting avian IAV RNA replication. We identified residue 313 in the viral nucleoprotein (NP) as the genetic determinant of BTN3A3 sensitivity (313F or, rarely, 313L in avian viruses) or evasion (313Y or 313V in human viruses). However, avian IAV serotypes, such as H7 and H9, that spilled over into humans also evade BTN3A3 restriction. In these cases, BTN3A3 evasion is due to substitutions (N, H or Q) in NP residue 52 that is adjacent to residue 313 in the NP structure[SUP]3[/SUP]. Thus, sensitivity or resistance to BTN3A3 is another factor to consider in the risk assessment of the zoonotic potential of avian influenza viruses.
This is a preview of subscription content.
Access through your institution
https://www.nature.com/articles/s41586-023-06261-8#citeas
__________________________________________________ ____________
A preview of this full-text is provided by Springer Nature. ResearchGate
Content available from Nature
... Abstract and Figures
Inluenza A viruses (IAVs) cause a substantial global health burden
and circulate both in humans and animal species, including domestic
poultry, pigs, dogs and horses. Wild aquatic birds are the main natu-
ral reservoir of IAVs4. Ducks, shorebirds, gulls and other waterbirds
harbour 16 haemagglutinin and 9 neuraminidase subtypes5. IAVs
from wild bird reservoirs can infect economically important birds,
such as chickens, turkeys, quail and other gallinaceous species and
domestic waterfowl 4. The population density of domestic birds and
the direct exposure to infected birds facilitates avian IAV spillovers
into susceptible mammals, including humans. Avian IAVs can also
further reassort (that is, exchange genome segments) with viruses
established in susceptible species resulting in the rich IAV genetic
diversity. In humans, the influenza pandemics of 1918, 1957, 1968 and
2009 were all caused by viruses containing genomic segments of
avian origin. ...
https://www.researchgate.net/public...the_zoonotic_potential_of_influenza_A_viruses