Phylogeography and Evolutionary History of Reassortant H9N2 Viruses with Potential Human Health Implications

Fusaro, Alice; Monne, Isabella; Salviato, Annalisa; Valastro, Viviana; Schivo, Alessia; Amarin, Nadim Mukhles; González, Carlos; Ismail, Mona H; Al-Ankari, Abdu-Rahman; Al-Blowi, Mohamed Hamad; Khan, Owais; Ali, Ali Safar Maken; Hedayati, Afshin; García, Juan García; Ziay, G.; Shoushtari, A; Qahtani, Kassem Nasser Al; Capua, Ilaria; Holmes, Edward C.; Cattoli, Giovanni

doi:10.1128/jvi.00219-11

Cited by 149 publications

(170 citation statements)

References 48 publications

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“…Although nearly all RNA viruses seem to experience very rapid evolutionary change-usually expressed as rates of nucleotide substitution per site-far lower rates are observed in some large double-stranded DNA (dsDNA) viruses. For example, the nucleotide substitution rates for variola virus and herpes simplex virus (dsDNA) have been reported to be as low as 9.32 Â 10 -6 and 3 Â 10 29 substitutions per site per year, respectively [6,7], and hence between three to six orders of magnitude lower than that of influenza virus A (negative-sense singlestranded RNA; 2ssRNA) at 4.1 Â 10 23 substitutions per site per year [8]. Overall, most RNA viruses seem to exhibit evolutionary rates of around 10 23 to 10 24 substitutions per site per year [9].…”

Section: Introductionmentioning

confidence: 99%

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

2014

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Time-scales of viral evolution and emergence have been studied widely, but are often poorly understood. Molecular analyses of viral evolutionary timescales generally rely on estimates of rates of nucleotide substitution, which vary by several orders of magnitude depending on the timeframe of measurement. We analysed data from all major groups of viruses and found a strong negative relationship between estimates of nucleotide substitution rate and evolutionary timescale. Strikingly, this relationship was upheld both within and among diverse groups of viruses. A detailed case study of primate lentiviruses revealed that the combined effects of sequence saturation and purifying selection can explain this time-dependent pattern of rate variation. Therefore, our analyses show that studies of evolutionary time-scales in viruses require a reconsideration of substitution rates as a dynamic, rather than as a static, feature of molecular evolution. Improved modelling of viral evolutionary rates has the potential to change our understanding of virus origins.

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Section: Introductionmentioning

confidence: 99%

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

2014

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“…H9N2 is a predominant subtype of AIVs circulating in poultry farms in Asia and the Middle East and has caused substantial economic losses over the past decade (3)(4)(5)(6)(7)(8)(9). Although a large amount of H9N2 vaccines, including inactivated and vectored vaccines, have been used in areas of endemicity, outbreaks caused by H9N2 AIVs are still not efficiently controlled.…”

mentioning

confidence: 99%

A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice

Teng

Shen

et al. 2016

J Virol

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H9N2 avian influenza virus (AIV) has an extended host range, but the molecular basis underlying H9N2 AIV transmission to mammals remains unclear. We isolated more than 900 H9N2 AIVs in our 3-year surveillance in live bird markets in China from 2009 to 2012. Thirty-seven representative isolates were selected for further detailed characterization. These isolates were categorized into 8 genotypes (B64 to B71) and formed a distinct antigenic subgroup. Three isolates belonging to genotype B69, which is a predominant genotype circulating in China, replicated efficiently in mice, while the viruses tested in parallel in other genotypes replicated poorly, although they, like the three B69 isolates, have a leucine at position 226 in the hemagglutinin (HA) receptor binding site, which is critical for binding human type sialic acid receptors. Further molecular and single mutation analysis revealed that a valine (V) residue at position 190 in HA is responsible for efficient replication of these H9N2 viruses in mice. The 190V in HA does not affect virus receptor binding specificity but enhances binding affinity to human cells and lung tissues from mouse and humans. All these data indicate that the 190V in HA is one of the important determinants for H9N2 AIVs to cross the species barrier to infect mammals despite multiple genes conferring adaptation and replication of H9N2 viruses in mammals. Our findings provide novel insights on understanding host range expansion of H9N2 AIVs. IMPORTANCE Influenza virus hemagglutinin (HA) is responsible for binding to host cell receptors and therefore influences the viral host rangeand pathogenicity in different species. We showed that the H9N2 avian influenza viruses harboring 190V in the HA exhibit enhanced virus replication in mice. Further studies demonstrate that 190V in the HA does not change virus receptor binding specificity but enhances virus binding affinity of the H9N2 virus to human cells and attachment to lung tissues from humans and mouse. Our findings suggest that more attention should be given to the H9N2 AIVs with HA-190V during surveillance due to their potential threat to mammals, including humans. Since the first isolate of an avian influenza virus (AIV) H9N2 subtype was reported in the United States in 1966, three distinct lineages of H9N2 viruses that caused outbreaks in domestic poultry in Asia have been identified (1, 2). H9N2 is a predominant subtype of AIVs circulating in poultry farms in Asia and the Middle East and has caused substantial economic losses over the past decade (3-9). Although a large amount of H9N2 vaccines, including inactivated and vectored vaccines, have been used in areas of endemicity, outbreaks caused by H9N2 AIVs are still not efficiently controlled. Importantly, H9N2 AIV has been reported to infect mammals, including humans, pigs, and dogs (10-13), indicating that it has an extended host range. It should be noted that several human infections with an H9N2 AIV have been recorded (14,15). Numerous human infections have also been confirm...

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“…This suggests a contribution from an H9N2 virus to the internal genes of the HPAI H5N1 virus that infected humans (10). Genetic drift has caused distinct lineages of H9N2 virus to emerge in Eurasia, and between three and five Eurasian H9N2 lineages have been proposed (11)(12)(13). Recent data have shown that H9N2 reassortment, together with adaptive mutations, can generate novel reassortant viruses that are more transmissible and more pathogenic in mammalian models than the parental viruses (14,15).…”

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Alternative Reassortment Events Leading to Transmissible H9N1 Influenza Viruses in the Ferret Model

Kimble

Angel

Wan

et al. 2014

J Virol

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Influenza A H9N2 viruses are common poultry pathogens that occasionally infect swine and humans. It has been shown previously with H9N2 viruses that reassortment can generate novel viruses with increased transmissibility. Here, we demonstrate the modeling power of a novel transfection-based inoculation system to select reassortant viruses under in vivo selective pressure. Plasmids containing the genes from an H9N2 virus and a pandemic H1N1 (pH1N1) virus were transfected into HEK 293T cells to potentially generate the full panel of possible H9 reassortants. These cells were then used to inoculate ferrets, and the population dynamics were studied. Two respiratory-droplet-transmissible H9N1 viruses were selected by this method, indicating a selective pressure in ferrets for the novel combination of surface genes. These results show that a transfection-based inoculation system is a fast and efficient method to model reassortment and highlight the risk of reassortment between H9N2 and pH1N1 viruses.

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Phylogeography and Evolutionary History of Reassortant H9N2 Viruses with Potential Human Health Implications

Cited by 149 publications

References 48 publications

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates

A Single Mutation at Position 190 in Hemagglutinin Enhances Binding Affinity for Human Type Sialic Acid Receptor and Replication of H9N2 Avian Influenza Virus in Mice

Alternative Reassortment Events Leading to Transmissible H9N1 Influenza Viruses in the Ferret Model

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