Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential

Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A.; Nakajima, N.; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F.; Takahashi, Keiichi; Fukuyama, Satoru; Tomita, Yuriko; Maher, Eileen A.; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C.; Smith, Derek J.; Kawaoka, Yoshihiro

doi:10.1016/j.chom.2014.05.006

Cited by 68 publications

(64 citation statements)

References 41 publications

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“…Having a lysine at position 627 of PB2 confers efficient replication to avian influenza viruses at 33°C and 37°C 83, 84 , enabling them to establish robust infections in mammals. Additionally, the PB2-627K mutation has recently been shown to increase the transmissibility of avian influenza viruses 85–87 .…”

Section: Viral Determinants Of Influenza Virus Host Rangementioning

confidence: 99%

Pandemic potential of avian influenza A (H7N9) viruses

Watanabe¹,

Watanabe²,

Maher³

et al. 2014

Trends in Microbiology

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Avian influenza viruses rarely infect humans, but the recently emerged avian H7N9 influenza viruses have caused sporadic infections in humans in China, resulting in 440 confirmed cases with 122 fatalities as of May 16, 2014. In addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with H7N9 viruses. These viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes that likely contribute to their ability to infect mammals. Here, we summarize the characteristic features of the novel H7N9 viruses and assess their pandemic potential.

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Section: Viral Determinants Of Influenza Virus Host Rangementioning

confidence: 99%

Pandemic potential of avian influenza A (H7N9) viruses

Watanabe¹,

Watanabe²,

Maher³

et al. 2014

Trends in Microbiology

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“…The most recent pandemic was the swine-origin influenza A H1N1 in 2009 (A(H1N1)2009) (Watanabe et al, 2014). Despite the large antigenic distance between the HA of A(H1N1)2009 and the HA of seasonal influenza virus strains (Garten et al, 2009), the impact of the pandemic was lower than expected because of pre-existing immunity in many adults.…”

Section: Introductionmentioning

confidence: 96%

Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic

Mesman

Westerhuis

Hulscher

et al. 2016

Journal of General Virology

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Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

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“…Virus samples were directly labeled with biotin (26) and then applied to the slide array. Slide scanning to detect virus bound to glycans was conducted as described previously (27). A complete list of glycans on the array is presented in Table S1 in the supplemental material.…”

Section: Cellsmentioning

confidence: 99%

Identification of Stabilizing Mutations in an H5 Hemagglutinin Influenza Virus Protein

Hanson

Imai

Hatta

et al. 2016

J Virol

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Highly pathogenic avian influenza viruses of the H5N1 subtype continue to circulate in poultry in Asia, Africa, and the Middle East. Recently, outbreaks of novel reassortant H5 viruses have also occurred in North America. Although the number of human infections with highly pathogenic H5N1 influenza viruses continues to rise, these viruses remain unable to efficiently transmit between humans. However, we and others have identified H5 viruses capable of respiratory droplet transmission in ferrets. Two experimentally introduced mutations in the viral hemagglutinin (HA) receptor-binding domain conferred binding to humantype receptors but reduced HA stability. Compensatory mutations in HA (acquired during virus replication in ferrets) were essential to restore HA stability. These stabilizing mutations in HA also affected the pH at which HA undergoes an irreversible switch to its fusogenic form in host endosomes, a crucial step for virus infectivity. To identify additional stabilizing mutations in an H5 HA, we subjected a virus library possessing random mutations in the ectodomain of an H5 HA (altered to bind humantype receptors) to three rounds of treatment at 50°C. We isolated several mutants that maintained their human-type receptorbinding preference but acquired an appreciable increase in heat stability and underwent membrane fusion at a lower pH; collectively, these properties may aid H5 virus respiratory droplet transmission in mammals. IMPORTANCEWe have identified mutations in HA that increase its heat stability and affect the pH that triggers an irreversible conformational change (a prerequisite for virus infectivity). These mutations were identified in the genetic background of an H5 HA protein that was mutated to bind to human cells. The ability to bind to human-type receptors, together with physical stability and an altered pH threshold for HA conformational change, may facilitate avian influenza virus transmission via respiratory droplets in mammals.

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Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential

Cited by 68 publications

References 41 publications

Pandemic potential of avian influenza A (H7N9) viruses

Pandemic potential of avian influenza A (H7N9) viruses

Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic

Identification of Stabilizing Mutations in an H5 Hemagglutinin Influenza Virus Protein

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