tetano
Editor, Senior Moderator
J Virol
. 2020 Oct 28;JVI.01066-20.
doi: 10.1128/JVI.01066-20. Online ahead of print.
Detection and Characterization of Swine-origin Influenza A(H1N1) Pandemic 2009 Viruses in Humans Following Zoonotic Transmission
Peter W Cook[SUP] 1 2 [/SUP], Thomas Stark[SUP] 1 [/SUP], Joyce Jones[SUP] 1 [/SUP], Rebecca Kondor[SUP] 1 [/SUP], Natosha Zanders[SUP] 1 [/SUP], Jeffrey Benfer[SUP] 3 [/SUP], Samantha Scott[SUP] 4 [/SUP], Yunho Jang[SUP] 1 [/SUP], Alicia Janas-Martindale[SUP] 5 [/SUP], Stephen Lindstrom[SUP] 1 [/SUP], Lenee Blanton[SUP] 1 [/SUP], John Schiltz[SUP] 5 [/SUP], Rachel Tell[SUP] 5 [/SUP], Richard Griesser[SUP] 4 [/SUP], Peter Shult[SUP] 4 [/SUP], Erik Reisdorf[SUP] 4 [/SUP], Tonya Danz[SUP] 4 [/SUP], Alicia Fry[SUP] 1 [/SUP], John Barnes[SUP] 1 [/SUP], Amy Vincent[SUP] 6 [/SUP], David E Wentworth[SUP] 1 [/SUP], C Todd Davis[SUP] 7 [/SUP]
Affiliations
Abstract
Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the United States swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as 'swine-origin' or 'human-origin' due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as 'swine-origin' variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 HA and NA genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses.IMPORTANCE Influenza virus infects a wide range of hosts resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and non-human hosts resulting in human and non-human origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that as these viruses not only circulate in swine hosts, but are continuing to evolve and distinguish themselves from previously circulating human-origin influenza viruses. The development of techniques for distinguishing human-origin and swine-origin viruses are necessary for the continued surveillance of influenza viruses. We show that unique genetic signatures can differentiate circulating swine-associated strains from circulating human-associated strains of influenza A(H1N1)pdm09, and these signatures can be used to enhance surveillance of swine-origin influenza.
. 2020 Oct 28;JVI.01066-20.
doi: 10.1128/JVI.01066-20. Online ahead of print.
Detection and Characterization of Swine-origin Influenza A(H1N1) Pandemic 2009 Viruses in Humans Following Zoonotic Transmission
Peter W Cook[SUP] 1 2 [/SUP], Thomas Stark[SUP] 1 [/SUP], Joyce Jones[SUP] 1 [/SUP], Rebecca Kondor[SUP] 1 [/SUP], Natosha Zanders[SUP] 1 [/SUP], Jeffrey Benfer[SUP] 3 [/SUP], Samantha Scott[SUP] 4 [/SUP], Yunho Jang[SUP] 1 [/SUP], Alicia Janas-Martindale[SUP] 5 [/SUP], Stephen Lindstrom[SUP] 1 [/SUP], Lenee Blanton[SUP] 1 [/SUP], John Schiltz[SUP] 5 [/SUP], Rachel Tell[SUP] 5 [/SUP], Richard Griesser[SUP] 4 [/SUP], Peter Shult[SUP] 4 [/SUP], Erik Reisdorf[SUP] 4 [/SUP], Tonya Danz[SUP] 4 [/SUP], Alicia Fry[SUP] 1 [/SUP], John Barnes[SUP] 1 [/SUP], Amy Vincent[SUP] 6 [/SUP], David E Wentworth[SUP] 1 [/SUP], C Todd Davis[SUP] 7 [/SUP]
Affiliations
- PMID: 33115872
- DOI: 10.1128/JVI.01066-20
Abstract
Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the United States swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as 'swine-origin' or 'human-origin' due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as 'swine-origin' variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 HA and NA genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses.IMPORTANCE Influenza virus infects a wide range of hosts resulting in illnesses that vary from asymptomatic cases to severe pneumonia and death. Viral transfer can occur between human and non-human hosts resulting in human and non-human origin viruses circulating in novel hosts. In this work, we have identified the first case of a swine-origin influenza A(H1N1)pdm09 virus resulting in a human infection. This shows that as these viruses not only circulate in swine hosts, but are continuing to evolve and distinguish themselves from previously circulating human-origin influenza viruses. The development of techniques for distinguishing human-origin and swine-origin viruses are necessary for the continued surveillance of influenza viruses. We show that unique genetic signatures can differentiate circulating swine-associated strains from circulating human-associated strains of influenza A(H1N1)pdm09, and these signatures can be used to enhance surveillance of swine-origin influenza.