Multiple amino acid substitutions involved in enhanced pathogenicity of LPAI H9N2 in mice

Zhang, Zongde; Hu, Sishun; Li, Zili; Wang, Xiliang; Liu, Mei; Guo, Zisheng; Li, Shaowen; Xiao, Yufei; Bi, Dingren; Jin, Hui

doi:10.1016/j.meegid.2011.07.025

Cited by 34 publications

(39 citation statements)

References 41 publications

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“…The T139A mutation has also been iden-tified in the mouse-adapted A/FM/1/47-MA(H1N1) strain (Brown and Bailly 1999; Smeenk and Brown 1994; Smeenk et al 1996). Changes in M1 and in M2 have also been observed during mouse adaptation of H2 (Govorkova et al 2000), H3N2 (Brown et al 2001; Ping et al 2010), and H9N2 (Zhang et al 2011) viruses, although the functional importance of these changes is unclear. Using reverse genetics, N30D and T215A in the M1 protein were shown to increase the virulence of H5N1 virus in mice (Fan et al 2009).…”

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

“…NA activity must balance HA activity for optimal viral entry and exit, and it is therefore not surprising that the NA segment affects mouse virulence (Gen et al 2013; Pappas et al 2008; Tumpey et al 2004; Zhang et al 2011). In some cases, enzymatic activity of NA has been linked to mouse virulence.…”

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

“…One of the most common changes as avian influenza viruses are adapted to mouse infection is an E627K change in PB2 (de Jong et al 2013; Kim et al 2010; Ping et al 2010; Song et al 2011; Tian et al 2012; Wang et al 2012; Wu et al 2009; Zhang et al 2011), and this change is strongly linked to increased mouse virulence in H5N1 (Chen et al 2007; Hatta et al 2001; Li et al 2009; Maines et al 2005) and H7N7 (Munster et al 2007) HPAI viruses, H7N9 LPAI viruses (Mok et al 2014; Zhang et al 2014), and the 1918 H1N1 (Qi et al 2012). Many H5N1 HPAIV and H7N9 LPAIV isolated from zoonotic human infections possess this substitution, whereas viruses isolated from avian species generally do not (Fonville et al 2013; Manz et al 2013).…”

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

“…Mouse-adaptive changes in the PB1 and PA genes include several that compensate for the lack of E627K in an avian-origin RNP complex, such as L472V and L598P in PB1 (Xu et al 2012). Multiple other substitutions in these genes that have been associated with changes in mouse virulence have been described (Hiromoto et al 2000; Ilyushina et al 2010; Liedmann et al 2013; Manz et al 2013; Ping et al 2011; Song et al 2013b; Zhang et al 2011). The mechanisms by which these substitutions affect mouse virulence are not known, although many of the mutations are at sites involved in the protein-protein interactions involved in polymerase complex assembly (Manz et al 2013; Ping et al 2011).…”

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

“…While NS1 is non-essential for viral replication in cultured cells (Garcia-Sastre et al 1998), it is critical for natural infection because of its ability to inhibit the host innate immune response (Donelan et al 2003) (reviewed in Hale et al 2008) through species-specific interactions with multiple host proteins (Rajsbaum et al 2012). Therefore, it is not surprising that mutations in NS1 are frequently observed during mouse adaptation of both human (Brown et al 2001; Forbes et al 2012; Ping et al 2011) and avian (Dankar et al 2011; Zhang et al 2011) influenza viruses. For example, adaptation of the human H3N2 virus to mice resulted in 12 different NS1 mutations, most of which enhanced the ability of the virus to block IFN induction in mice (Forbes et al 2012).…”

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

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Molecular Determinants of Influenza Virus Pathogenesis in Mice

Kamal

Katz

York

2014

Current Topics in Microbiology and Immunology

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Mice are widely used for studying influenza virus pathogenesis and immunology because of their low cost, the wide availability of mouse-specific reagents, and the large number of mouse strains available, including knockout and transgenic strains. However, mice do not fully recapitulate the signs of influenza infection of humans: transmission of influenza between mice is much less efficient than in humans, and influenza viruses often require adaptation before they are able to efficiently replicate in mice. In the process of mouse adaptation, influenza viruses acquire mutations that enhance their ability to attach to mouse cells, replicate within the cells, and suppress immunity, among other functions. Many such mouse-adaptive mutations have been identified, covering all 8 genomic segments of the virus. Identification and analysis of these mutations have provided insight into the molecular determinants of influenza virulence and pathogenesis, not only in mice but also in humans and other species. In particular, several mouse-adaptive mutations of avian influenza viruses have proved to be general mammalian-adaptive changes that are potential markers of pre-pandemic viruses. As well as evaluating influenza pathogenesis, mice have also been used as models for evaluation of novel vaccines and anti-viral therapies. Mice can be a useful animal model for studying influenza biology as long as differences between human and mice infections are taken into account.

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Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

Section: Viral Determinants Of Influenza Virulence In Micementioning

confidence: 99%

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Molecular Determinants of Influenza Virus Pathogenesis in Mice

Kamal

Katz

York

2014

Current Topics in Microbiology and Immunology

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Low‐pathogenicity avian influenza

Pérez

Wit

2016

Animal Influenza

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Phylogenetic and genetic characterization of influenza A H9N2 viruses isolated from backyard poultry in selected farms in Ghana

Kotey

Asante

Adusei-Poku

et al. 2022

Veterinary Medicine & Sci

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Introduction Avian influenza viruses (AIV) cause significant economic losses to poultry farmers worldwide. These viruses have the ability to spread rapidly, infect entire poultry flocks, and can pose a threat to human health. The National Influenza Centre (NIC) at the Noguchi Memorial Institute for Medical Research in collaboration with the Ghana Armed forces (GAF) and the U.S. Naval Medical Research Unit No. 3, Ghana Detachment (NAMRU‐3) performs biannual surveillance for influenza viruses among poultry at military barracks throughout Ghana. This study presents poultry surveillance data from the years 2017 to 2019. Methodology Tracheal and cloacal swabs from sick and healthy poultry were collected from the backyards of GAF personnel living quarters and transported at 4°C to the NIC. Viral ribonucleic acid (RNA) was isolated and analyzed for the presence of influenza viruses using real‐time polymerase chain reaction (PCR) assays. Viral nucleic acids extracted from influenza A‐positive specimens were sequenced using universal influenza A‐specific primers. Results Influenza A H9N2 virus was detected in 11 avian species out of 2000 samples tested. Phylogenetic analysis of viral haemagglutinin (HA) protein confirms the possibility of importation of viruses from North Africa and Burkina Faso. Although the detected viruses possess molecular markers of virulence and mammalian host adaptation, the HA cleavage site anlaysis confirmed low pathogenicity of the viruses. Conclusions These findings confirm the ongoing spread of H9 viruses among poultry in Ghana. Poultry farmers need to be vigilant for sick birds and take the appropriate public health steps to limit the spread to other animals and spillover to humans.

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Multiple amino acid substitutions involved in enhanced pathogenicity of LPAI H9N2 in mice

Cited by 34 publications

References 41 publications

Molecular Determinants of Influenza Virus Pathogenesis in Mice

Molecular Determinants of Influenza Virus Pathogenesis in Mice

Low‐pathogenicity avian influenza

Phylogenetic and genetic characterization of influenza A H9N2 viruses isolated from backyard poultry in selected farms in Ghana

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