scholarly journals Adaptation of H9N2 Influenza Viruses to Mammalian Hosts: A Review of Molecular Markers

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 541 ◽  
Author(s):  
Xiangjie Sun ◽  
Jessica A. Belser ◽  
Taronna R. Maines
Keyword(s):  
Animal Models ◽  
Avian Influenza ◽  
Mammalian Cells ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Phenotypic Characterization ◽  
Pandemic Preparedness ◽  
Avian Influenza Viruses ◽  
Eurasian Lineage

As the number of human infections with avian and swine influenza viruses continues to rise, the pandemic risk posed by zoonotic influenza viruses cannot be underestimated. Implementation of global pandemic preparedness efforts has largely focused on H5 and H7 avian influenza viruses; however, the pandemic threat posed by other subtypes of avian influenza viruses, especially the H9 subtype, should not be overlooked. In this review, we summarize the literature pertaining to the emergence, prevalence and risk assessment of H9N2 viruses, and add new molecular analyses of key mammalian adaptation markers in the hemagglutinin and polymerase proteins. Available evidence has demonstrated that H9N2 viruses within the Eurasian lineage continue to evolve, leading to the emergence of viruses with an enhanced receptor binding preference for human-like receptors and heightened polymerase activity in mammalian cells. Furthermore, the increased prevalence of certain mammalian adaptation markers and the enhanced transmissibility of selected viruses in mammalian animal models add to the pandemic risk posed by this virus subtype. Continued surveillance of zoonotic H9N2 influenza viruses, inclusive of close genetic monitoring and phenotypic characterization in animal models, should be included in our pandemic preparedness efforts.

scholarly journals The Polymerase Acidic Protein Gene of Influenza A Virus Contributes to Pathogenicity in a Mouse Model

2009 ◽  
Vol 83 (23) ◽  
pp. 12325-12335 ◽  
Author(s):  
Min-Suk Song ◽  
Philippe Noriel Q. Pascua ◽  
Jun Han Lee ◽  
Yun Hee Baek ◽  
Ok-Jun Lee ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Mammalian Cells ◽  
Influenza A ◽  
Lethal Dose ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Viral Gene ◽  
Avian Influenza Viruses ◽  
Range Restriction ◽  
Viral Genes

ABSTRACT Adaptation of influenza A viruses to a new host species usually involves the mutation of one or more of the eight viral gene segments, and the molecular basis for host range restriction is still poorly understood. To investigate the molecular changes that occur during adaptation of a low-pathogenic avian influenza virus subtype commonly isolated from migratory birds to a mammalian host, we serially passaged the avirulent wild-bird H5N2 strain A/Aquatic bird/Korea/W81/05 (W81) in the lungs of mice. The resulting mouse-adapted strain (ma81) was highly virulent (50% mouse lethal dose = 2.6 log10 50% tissue culture infective dose) and highly lethal. Nonconserved mutations were observed in six viral genes (those for PB2, PB1, PA, HA, NA, and M). Reverse genetic experiments substituting viral genes and mutations demonstrated that the PA gene was a determinant of the enhanced virulence in mice and that a Thr-to-Iso substitution at position 97 of PA played a key role. In growth kinetics studies, ma81 showed enhanced replication in mammalian but not avian cell lines; the PA97I mutation in strain W81 increased its replicative fitness in mice but not in chickens. The high virulence associated with the PA97I mutation in mice corresponded to considerably enhanced polymerase activity in mammalian cells. Furthermore, this characteristic mutation is not conserved among avian influenza viruses but is prevalent among mouse-adapted strains, indicating a host-dependent mutation. To our knowledge, this is the first study that the isoleucine residue at position 97 in PA plays a key role in enhanced virulence in mice and is implicated in the adaptation of avian influenza viruses to mammalian hosts.

scholarly journals Resurrected ancestral influenza A viruses recapitulate the avian-to-mammalian adaptation of European avian-like swine influenza virus

2021 ◽  
Author(s):  
Wen Su ◽  
Rhodri Harfoot ◽  
Yvonne Su ◽  
Jennifer DeBeauchamp ◽  
Udayan Joseph ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Influenza A ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Mammalian Host ◽  
Influenza A Viruses ◽  
Sequence Reconstruction

Abstract The emergence of a pandemic influenza virus may be better anticipated if we better understand the evolutionary steps taken by avian influenza viruses as they adapt to mammals. We used ancestral sequence reconstruction to resurrect viruses representing initial adaptive stages of the European avian-like H1N1 virus as it transitioned from avian to swine hosts. We demonstrate that efficient transmissibility in pigs was gained through stepwise adaptation after 1983. These time-dependent adaptations resulted in changes in hemagglutinin receptor binding specificity and increased viral polymerase activity. An NP-R351K mutation under strong positive selection increased the transmissibility of a reconstructed virus. The stepwise-adaptation of a wholly avian influenza virus to a mammalian host suggests a window where targeted intervention may have highest impact. Successful intervention will, however, require strategic coordination of surveillance and risk assessment activities to identify these adapting viruses and guide pandemic preparedness resources.

scholarly journals The PB1 Gene from H9N2 Avian Influenza Virus Showed High Compatibility and Increased Mutation Rate after Reassorting with a Human H1N1 Influenza Virus

2021 ◽  
Author(s):  
Hongrui Cui ◽  
Guangsheng Che ◽  
Mart CM de Jong ◽  
Xuesong Li ◽  
Qinfang Liu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
H1n1 Virus ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Luciferase Reporter ◽  
Avian Influenza Viruses ◽  
Reassortant Virus ◽  
Rnp Complex ◽  
Reassortant Viruses

Abstract BackgroundReassortment between human and avian influenza viruses (AIV) may result in novel viruses with new characteristics that may threaten human health when causing the next flu pandemic. A particular risk may be posed by avian influenza viruses of subtype H9N2 that are currently massively circulating in domestic poultry in Asia and have been shown to infect humans. In this study, we investigate the characteristics and compatibility of a human H1N1 virus with avian H9N2 derived genes. MethodsThe polymerase activity of the viral ribonucleoprotein (RNP) complex from different reassortments was tested in luciferase reporter assays. Reassortant viruses were generated by reverse genetics in which genes of the human WSN-H1N1 virus (A/WSN/1933) were replaced by genes of the avian A2093-H9N2 virus (A/chicken/Jiangsu/A2093/2011). We replaced both the Hemagglutinin (HA) and Neuraminidase (NA) genes in combination with one of the genes involved in the RNP complex (either PB2, PB1, PA or NP). The growth kinetics and virulence of reassortant viruses were tested on cell lines and mice. The reassortant viruses were then passaged for five generations in MDCK cells and mice lungs. The HA gene of progeny viruses from different passaging paths was analyzed using Next Generation Sequencing (NGS). ResultsWe discovered that the avian PB1 gene increased the polymerase activity of the RNP complex. Reassortant viruses were able to replicate in MDCK and DF1 cells and mice. Analysis of the NGS data showed a higher substitution rate for the PB1-reassortant virus. In particular, for the PB1-reassortant virus, increased virulence for mice was measured by increased body weight loss after infection in mice. ConclusionsThe higher polymerase activity and increased mutation frequency measured for the PB1-reassortant virus suggests that the avian PB1 gene may drive the evolution and adaptation of novel reassortant viruses to the human host. This study provides novel insights in the characteristics of novel viruses that may arise by reassortment of human and avian influenza viruses. Surveillance for infections with H9N2 viruses and the emergence of novel reassortant viruses in humans is important for pandemic preparedness.

Double mutations in the H9N2 avian influenza virus PB2 gene act cooperatively to increase viral host adaptation and replication for human infections

2021 ◽  
Vol 102 (6) ◽  
Author(s):  
Emad Mohamed Elgendy ◽  
Yasuha Arai ◽  
Norihito Kawashita ◽  
Ayana Isobe ◽  
Tomo Daidoji ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Polymerase Activity ◽  
Host Adaptation ◽  
Influenza Viruses ◽  
Human Adaptation ◽  
Avian Influenza Viruses ◽  
Human Virus ◽  
H9n2 Avian Influenza Virus ◽  
Human Infections ◽  
Virus Isolates

Avian H9N2 influenza viruses in East Asia are genetically diversified and multiple genotypes (A-W) have been established in poultry. Genotype S strains are currently the most prevalent strains, have caused many human infections and pose a public health threat. In this study, human adaptation mutations in the PB2 polymerase in genotype S strains were identified by database screening. Several PB2 double mutations were identified that acted cooperatively to produce higher genotype S virus polymerase activity and replication in human cells than in avian cells and to increase viral growth and virulence in mice. These mutations were chronologically and phylogenetically clustered in a new group within genotype S viruses. Most of the relevant human virus isolates carry the PB2-A588V mutation together with another PB2 mutation (i.e. K526R, E627V or E627K), indicating a host adaptation advantage for these double mutations. The prevalence of PB2 double mutations in human H9N2 virus isolates has also been found in genetically related human H7N9 and H10N8 viruses. These results suggested that PB2 double mutations in viruses in the field acted cooperatively to increase human adaptation of the currently prevalent H9N2 genotype S strains. This may have contributed to the recent surge of H9N2 infections and may be applicable to the human adaptation of several other avian influenza viruses. Our study provides a better understanding of the human adaptation pathways of genetically related H9N2, H7N9 and H10N8 viruses in nature.

scholarly journals NS1 Proteins of Avian Influenza A Viruses Can Act as Antagonists of the Human Alpha/Beta Interferon Response

2006 ◽  
Vol 81 (5) ◽  
pp. 2318-2327 ◽  
Author(s):  
A. Hayman ◽  
S. Comely ◽  
A. Lackenby ◽  
L. C. S. Hartgroves ◽  
S. Goodbourn ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Mammalian Cells ◽  
Influenza A ◽  
Influenza Viruses ◽  
Type I ◽  
Type I Ifn ◽  
Human Influenza ◽  
Avian Influenza Viruses ◽  
Range Restriction ◽  
Host Range Restriction

ABSTRACT Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-β promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-β induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-β induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.

scholarly journals Different Pathogenicity and Transmissibility of Goose-Origin H5N6 Avian Influenza Viruses in Chickens

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 612 ◽  
Author(s):  
Kun Mei ◽  
Yang Guo ◽  
Xuhui Zhu ◽  
Nannan Qu ◽  
Jianni Huang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Guangdong Province ◽  
Influenza Viruses ◽  
Characteristic Analysis ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Recombinant Viruses ◽  
Pathogenic Avian Influenza ◽  
Eurasian Lineage

Highly pathogenic avian influenza H5N6 viruses have been circulating in poultry in Asia since 2013 and producing serious diseases in chickens. Here, we analyzed the genetic properties of 10 H5N6 subtypes AIVs from geese in 2015–2016 in Guangdong province. Phylogenic analysis showed that all HA genes of the 10 viruses belonged to clade 2.3.4.4, and their genes including HA, PA, PB1, M, NP, and NS all derived from Mix-like 1 (CH, VN, LS). Their PB2 genes come from Mix-like 2 (CH, VN, JP). The NA genes were classified into a Eurasian lineage. Therefore, the 10 viruses likely originate from the same ancestor and were all recombinant viruses between different genotypes. We selected A/Goose/Guangdong/GS144/2015(H5N6) (GS144) and A/Goose/Guangdong/GS148/2016(H5N6) (GS148) viruses to inoculate 5-week-old chickens intranasally with 104 EID50/0.1 mL dose intranasally to assess their pathogenicity and transmissibility. Inoculated chickens showed that the GS144 virus caused systematic infection with a lethality of 100%, but the lethality of GS148 virus was 0%. The two viruses were efficiently transmitted to contact chickens. The lethality of GS144 and GS148 virus in contact with chickens was 87.5% and 0%, respectively, which suggests that the transmissibility of GS144 virus was stronger than GS148 virus in chickens. Thus, different H5N6 viruses from the same waterfowl can show different pathogenicity and transmissibility in chickens. Continued surveillance and characteristic analysis of the H5N6 viruses will help us to keep abreast of evolution and variation in avian influenza viruses in the future.

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