Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza

ABSTRACTSwine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression.IMPORTANCEInfluenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.

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The neuraminidase and matrix genes of the 2009 pandemic influenza H1N1 virus cooperate functionally to facilitate efficient replication and transmissibility in pigs

Journal of General Virology ◽

10.1099/vir.0.040535-0 ◽

2012 ◽

Vol 93 (6) ◽

pp. 1261-1268 ◽

Cited By ~ 26

Author(s):

Wenjun Ma ◽

Qinfang Liu ◽

Bhupinder Bawa ◽

Chuanling Qiao ◽

Wenbao Qi ◽

...

Keyword(s):

Influenza A ◽

H1n1 Virus ◽

Swine Influenza ◽

Influenza Viruses ◽

Pandemic H1n1 ◽

Efficient Replication ◽

Pandemic Influenza H1n1 ◽

The Right ◽

Six Genes

The 2009 pandemic H1N1 virus (pH1N1) contains neuraminidase (NA) and matrix (M) genes from Eurasian avian-like swine influenza viruses (SIVs), with the remaining six genes from North American triple-reassortant SIVs. To characterize the role of the pH1N1 NA and M genes in pathogenesis and transmission, their impact was evaluated in the background of an H1N1 triple-reassortant (tr1930) SIV in which the HA (H3) and NA (N2) of influenza A/swine/Texas/4199-2/98 virus were replaced with those from the classical H1N1 A/swine/Iowa/15/30 (1930) virus. The laboratory-adapted 1930 virus did not shed nor transmit in pigs, but tr1930 was able to shed in infected pigs. The NA, M or both genes of the tr1930 virus were then substituted by those of pH1N1. The resulting virus with both NA and M from pH1N1 grew to significantly higher titre in cell cultures than the viruses with single NA or M from pH1N1. In a pig model, only the virus containing both NA and M from pH1N1 was transmitted to and infected sentinels, whereas the viruses with single NA or M from pH1N1 did not. These results demonstrate that the right combination of NA and M genes is critical for the replication and transmissibility of influenza viruses in pigs.

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The substitution of T271A in PB2 protein could enhance the infectivity and pathogenicity of Eurasian avian-like H1N1 swine influenza viruses in mice

10.21203/rs.3.rs-27732/v1 ◽

2020 ◽

Author(s):

Zhaomin Feng ◽

Wenfei Zhu ◽

Lijuan Zhou ◽

Yongkun Chen ◽

Xiyan Li ◽

...

Keyword(s):

H1n1 Virus ◽

Swine Influenza ◽

Polymerase Activity ◽

Influenza Viruses ◽

Pandemic H1n1 ◽

Recombinant Viruses ◽

Avian Cell ◽

Molecular Makers

Abstract BackgroundCurrently, Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs) are widely prevalent in pigs in China, with sporadic human cases reported as well. As one of the key molecular makers detected in avian H5N1 and H 7N9 viruses and pandemic H1N1 2009 virus, contributions of T271A in PB2 protein to the EA H1N1 viruses are still unknown. In this study, we investigated the effects of residue 271 in PB2 protein on the viral properties of EA H1N1 viruses.MethodsInfectivity, replication, virulence and pathogenicity of the recombinant viruses containing A or T in position 271 in PB2 protein were studied in cells and mice.ResultsThe results showed that the substitution PB2-T271A increased the viral replication in mammalian and avian cell lines. In addition, the mutation enhanced the viral infectivity, virulence and pathogenicity in mice. The viral titers of lung tissue in the rgHuN271A virus were higher than that of the rgHuN271T at 1, 4, and 7 dpi. The MID50 of the rgHuN271A and rgHuN271T virus were 101.1 TCID50 and 101.9 TCID50, respectively. Besides, the substitution of PB2-T271A enhanced the viral polymerase activity in mammalian cells.ConclusionsThe pathogenicity and replication of EA H1N1 virus containing 271A in PB2 protein were higher than the EA H1N1 virus containing 271T in PB2 protein in vivo and in vitro. Therefore, the PB2-T271A mutation should be continually monitored in influenza viruses circulating in pigs and humans.

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North American Triple Reassortant and Eurasian H1N1 Swine Influenza Viruses Do Not Readily Reassort to Generate a 2009 Pandemic H1N1-Like Virus

mBio ◽

10.1128/mbio.00919-13 ◽

2014 ◽

Vol 5 (2) ◽

Cited By ~ 11

Author(s):

Wenjun Ma ◽

Qinfang Liu ◽

Chuanling Qiao ◽

Gustavo del Real ◽

Adolfo García-Sastre ◽

...

Keyword(s):

Cell Cultures ◽

North American ◽

Influenza A ◽

H1n1 Virus ◽

Rare Event ◽

Swine Influenza ◽

Influenza Viruses ◽

Pandemic H1n1 ◽

Continuous Cell Lines ◽

Reassortant Viruses

ABSTRACTThe 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment.IMPORTANCEThe 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of influenza A virus.

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A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies

Vaccines ◽

10.3390/vaccines6030064 ◽

2018 ◽

Vol 6 (3) ◽

pp. 64 ◽

Cited By ~ 5

Author(s):

Sun-Young Sunwoo ◽

Michael Schotsaert ◽

Igor Morozov ◽

Anne Davis ◽

Yuhao Li ◽

...

Keyword(s):

Influenza Virus ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Influenza Viruses ◽

Pig Model ◽

Maternal Antibodies ◽

Control Group ◽

Infection Model ◽

Influenza B ◽

Pandemic H1n1

The antigenically conserved hemagglutinin stalk region is a target for universal influenza virus vaccines since antibodies against it can provide broad protection against influenza viruses of different subtypes. We tested a universal influenza virus vaccination regimen based on sequential immunization with chimeric hemagglutinin (HA) containing viruses in a swine influenza virus pig model with maternal antibodies against pandemic H1N1. Vaccines were administered as live attenuated virus or inactivated influenza virus split vaccine (+/− Emulsigen adjuvant). As controls, we included groups that received trivalent inactivated influenza vaccine that contained pandemic H1N1 antigens, inactivated adjuvanted H1N2 vaccine (control group for vaccine associated enhanced respiratory disease in the pig model) or mock-vaccination. No induction of H1 head or stalk-specific antibody responses was observed upon vaccination, while responses against H3 and influenza B HA were elicited in the group vaccinated with the trivalent vaccine. Four weeks post vaccination, pigs were intratracheally challenged with pandemic H1N1 virus and euthanized 5 days after challenge. Despite the lack of detectable anti-stalk immunity, the chimeric hemagglutinin vaccine resulted in better clinical outcomes compared to control groups.

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Cross-protection between antigenically distinct H1N1 swine influenza viruses from Europe and North America

Influenza and Other Respiratory Viruses ◽

10.1111/j.1750-2659.2010.00164.x ◽

2010 ◽

Vol 5 (2) ◽

pp. 115-122 ◽

Cited By ~ 19

Author(s):

Annebel R. De Vleeschauwer ◽

Sjouke G. Van Poucke ◽

Alexander I. Karasin ◽

Christopher W. Olsen ◽

Kristien Van Reeth

Keyword(s):

North America ◽

Swine Influenza ◽

Influenza Viruses ◽

Cross Protection

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Cluster analysis of the origins of the new influenza A(H1N1) virus

Eurosurveillance ◽

10.2807/ese.14.21.19224-en ◽

2009 ◽

Vol 14 (21) ◽

Cited By ~ 14

Author(s):

A Solovyov ◽

G Palacios ◽

T Briese ◽

W I Lipkin ◽

R Rabadan

Keyword(s):

Cluster Analysis ◽

Influenza A ◽

H1n1 Virus ◽

Swine Influenza ◽

The United States ◽

Influenza Viruses ◽

World Health ◽

Influenza A H1n1 ◽

The World ◽

Health Organization

In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia.

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Lack of cross-protection between European H1N1 and H1N2 swine influenza viruses

International Congress Series ◽

10.1016/s0531-5131(01)00345-4 ◽

2001 ◽

Vol 1219 ◽

pp. 341-345 ◽

Cited By ~ 1

Author(s):

Kristien Van Reeth ◽

Sophie De Clercq ◽

Maurice Pensaert

Keyword(s):

Swine Influenza ◽

Influenza Viruses ◽

Cross Protection

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Seroconversion to Pandemic (H1N1) 2009 Virus and Cross-Reactive Immunity to Other Swine Influenza Viruses

Emerging Infectious Diseases ◽

10.3201/eid1710.110629 ◽

2011 ◽

Vol 17 (10) ◽

pp. 1897-1899 ◽

Cited By ~ 11

Author(s):

Ranawaka A.P.M. Perera ◽

Steven Riley ◽

Siu K. Ma ◽

Hua-Chen Zhu ◽

Yi Guan ◽

...

Keyword(s):

Swine Influenza ◽

Influenza Viruses ◽

Pandemic H1n1 ◽

Pandemic H1n1 2009

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A North American H7N3 Influenza Virus Supports Reassortment with 2009 Pandemic H1N1 and Induces Disease in Mice without Prior Adaptation

Journal of Virology ◽

10.1128/jvi.02761-15 ◽

2016 ◽

Vol 90 (9) ◽

pp. 4796-4806 ◽

Cited By ~ 7

Author(s):

Graham D. Williams ◽

Amelia K. Pinto ◽

Brittany Doll ◽

Adrianus C. M. Boon

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

North American ◽

H1n1 Virus ◽

Influenza Viruses ◽

Pandemic H1n1 ◽

Reassortant Viruses ◽

H7n3 Virus ◽

Prior Adaptation

ABSTRACTReassortment between H5 or H9 subtype avian and mammalian influenza A viruses (IAV) can generate a novel virus that causes disease and transmits between mammals. Such information is currently not available for H7 subtype viruses. We evaluated the ability of a low-pathogenicity North American avian H7N3 virus (A/shorebird/Delaware/22/2006) to reassort with mammalian or avian viruses using a plasmid-based competition assay. In addition to genome segments derived from an avian H7N9 virus, the H7N3 virus reassorted efficiently with the PB2, NA, and M segments from the 2009 pandemic H1N1 (PH1N1) virus.In vitroandin vivoevaluation of the H7N3:PH1N1 (7 + 1) reassortant viruses revealed that the PB2, NA, or M segments fromPH1N1 largely do not attenuate the H7N3 virus, whereas the PB1, PA, NP, or NS genome segments fromPH1N1 do. Additionally, we assessed the functionality of the H7N3:PH1N1 7 + 1 reassortant viruses by measuring the inflammatory responsein vivo. We found that infection with wild-type H7N3 resulted in increased inflammatory cytokine production relative to that seen with thePH1N1 strain and that the increase was further exacerbated by substitution ofPH1N1 PB2 but not NA or M. Finally, we assessed if any adaptations occurred in the individually substituted segments afterin vivoinoculation and found no mutations, suggesting thatPH1N1 PB2, NA, and M are genetically stable in the background of this H7N3 virus. Taking the data together, we demonstrate that a North American avian H7N3 IAV is genetically and functionally compatible with multiple gene segments from the 2009 pandemic influenza virus strain without prior adaptation.IMPORTANCEThe 2009 pandemic H1N1 virus continues to circulate and reassort with other influenza viruses, creating novel viruses with increased replication and transmission potential in humans. Previous studies have found that this virus can also reassort with H5N1 and H9N2 avian influenza viruses. We now show that several genome segments of the 2009 H1N1 virus are also highly compatible with a low-pathogenicity avian H7N3 virus and that these reassortant viruses are stable and not attenuated in an animal model. These results highlight the potential for reassortment of H1N1 viruses with avian influenza virus and emphasize the need for continued surveillance of influenza viruses in areas of cocirculation between avian, human, and swine viruses.

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