In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity

Chen, Limei; Blixt, Ola; Stevens, James; Lipatov, A. S.; Davis, C. Todd; Collins, Brian E.; Cox, Nancy J.; Paulson, James C.; Donis, Ruben O.

doi:10.1016/j.virol.2011.10.006

Cited by 185 publications

(221 citation statements)

References 54 publications

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“…Although H5N1 mutants and reassortants have been shown to be transmissible in ferrets or guinea pigs (14,33,35,36), none of the naturally occurring H5N1 viruses is transmissible via respiratory droplet in these animal models. Certain H7N9 viruses are transmissible in ferrets (15,40), but their circulation so far is geographically restricted.…”

Section: Discussionmentioning

confidence: 98%

Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses

Yang

Chen

Qiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

104

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Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we performed extensive influenza surveillance in pigs in China and isolated 228 influenza viruses from 36,417 pigs. We found that 139 of the 228 strains from pigs in 10 provinces in China belong to the EAH1N1 lineage. These viruses formed five genotypes, with two distinct antigenic groups, represented by A/swine/Guangxi/18/2011 and A/swine/Guangdong/104/2013, both of which are antigenically and genetically distinct from the current human H1N1 viruses. Importantly, the EAH1N1 SIVs preferentially bound to human-type receptors, and 9 of the 10 tested viruses transmitted in ferrets by respiratory droplet. We found that 3.6% of children (≤10 y old), 0% of adults, and 13.4% of elderly adults (≥60 y old) had neutralization antibodies (titers ≥40 in children and ≥80 in adults) against the EAH1N1 A/swine/Guangxi/18/2011 virus, but none of them had such neutralization antibodies against the EAH1N1 A/swine/Guangdong/104/2013 virus. Our study shows the potential of EAH1N1 SIVs to transmit efficiently in humans and suggests that immediate action is needed to prevent the efficient transmission of EAH1N1 SIVs to humans.

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Section: Discussionmentioning

confidence: 98%

Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses

Yang

Chen

Qiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

104

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“…4 were isolated so that their HA genes could be sequenced and HA activation pH values measured. Bar charts for each of the four cages (5)(6)(7)(8) show the proportion of mutations with each residue at positions HA1-17 and HA2-106 over the course of infection. Proportions were determined by nextgeneration sequencing.…”

Section: Discussionmentioning

confidence: 99%

“…Although these traits appear to be necessary for airborne transmissibility of influenza viruses, they do not appear to be sufficient. For example, H5N1 viruses engineered to have these traits were not airtransmissible among ferrets until a mutation increased HA thermostability and lowered the HA activation pH (6)(7)(8). The importance of HA stabilization in supporting the adaptation of influenza viruses to humans or enabling a human pandemic is not completely understood.…”

mentioning

confidence: 99%

Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein

Russier

Yang

Rehg

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

210

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Influenza pandemics require that a virus containing a hemagglutinin (HA) surface antigen previously unseen by a majority of the population becomes airborne-transmissible between humans. Although the HA protein is central to the emergence of a pandemic influenza virus, its required molecular properties for sustained transmission between humans are poorly defined. During virus entry, the HA protein binds receptors and is triggered by low pH in the endosome to cause membrane fusion; during egress, HA contributes to virus assembly and morphology. In 2009, a swine influenza virus (pH1N1) jumped to humans and spread globally. Here we link the pandemic potential of pH1N1 to its HA acid stability, or the pH at which this one-time-use nanomachine is either triggered to cause fusion or becomes inactivated in the absence of a target membrane. In surveillance isolates, our data show HA activation pH values decreased during the evolution of H1N1 from precursors in swine (pH 5.5–6.0), to early 2009 human cases (pH 5.5), and then to later human isolates (pH 5.2–5.4). A loss-of-function pH1N1 virus with a destabilizing HA1-Y17H mutation (pH 6.0) was less pathogenic in mice and ferrets, less transmissible by contact, and no longer airborne-transmissible. A ferret-adapted revertant (HA1-H17Y/HA2-R106K) regained airborne transmissibility by stabilizing HA to an activation pH of 5.3, similar to that of human-adapted isolates from late 2009–2014. Overall, these studies reveal that a stable HA (activation pH ≤ 5.5) is necessary for pH1N1 influenza virus pathogenicity and airborne transmissibility in ferrets and is associated with pandemic potential in humans.

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“…It is known that in the human respiratory tract, NeuAc␣2,6-Gal is distributed on the upper respiratory tract and, in contrast, NeuAc␣2,3-Gal is found in the lower respiratory tract (20). It has been reported that the ␣2-3 SA-specific highly pathogenic avian influenza virus (H5N1) acquired increased affinity for human type receptors (␣2-6 SAs) by amino acid substitutions in hemagglutinin (HA) (21). This mutant H5N1 was shown to be transmissible only via direct contact in the ferret model (21).…”

Section: H Uman Enterovirus 68 (Ev68) (Species Human Enterovirus D;mentioning

confidence: 99%

“…It has been reported that the ␣2-3 SA-specific highly pathogenic avian influenza virus (H5N1) acquired increased affinity for human type receptors (␣2-6 SAs) by amino acid substitutions in hemagglutinin (HA) (21). This mutant H5N1 was shown to be transmissible only via direct contact in the ferret model (21). Moreover, the mutant H5N1 with affinity for human type receptors acquired transmissibility via respiratory droplets by introducing human N2 neuraminidase (NA) (21).…”

Section: H Uman Enterovirus 68 (Ev68) (Species Human Enterovirus D;mentioning

confidence: 99%

Antigenic and Receptor Binding Properties of Enterovirus 68

Imamura

Okamoto

Nakakita

et al. 2014

J Virol

114

127

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Increased detection of enterovirus 68 (EV68) among patients with acute respiratory infections has been reported from different parts of the world in the late 2000s since its first detection in pediatric patients with lower-respiratory-tract infections in 1962. However, the underlying molecular mechanisms for this trend are still unknown. We therefore aimed to study the antigenicity and receptor binding properties of EV68 detected in recent years in comparison to the prototype strain of EV68, the Fermon strain. We first performed neutralization (NT) and hemagglutination inhibition (HI) tests using antisera generated for EV68 strains detected in recent years. We found that the Fermon strain had lower HI and NT titers than recently detected EV68 strains. The HI and NT titers were also significantly different between strains of different genetic lineages among recently detected EV68 strains. We further studied receptor binding specificities of EV68 strains for sialyloligosaccharides using glycan array analysis. In glycan array analysis, all tested EV68 strains showed affinity for ␣2-6-linked sialic acids (␣2-6 SAs) compared to ␣2-3 SAs. Our study demonstrates that emergence of strains with different antigenicity is the possible reason for the increased detection of EV68 in recent years. Additionally, we found that EV68 preferably binds to ␣2-6 SAs, which suggests that EV68 might have affinity for the upper respiratory tract. IMPORTANCE Numbers of cases of enterovirus 68 (EV68) infection in different parts of the world increased significantly in the late 2000s.We studied the antigenicity and receptor binding properties of recently detected EV68 strains in comparison to the prototype strain of EV68, Fermon. The hemagglutination inhibition (HI) and neutralization (NT) titers were significantly different between strains of different genetic lineages among recently detected EV68 strains. We further studied receptor binding specificities of EV68 strains for sialyloligosaccharides using glycan array analysis, which showed affinity for ␣2-6-linked sialic acids (␣2-6 SAs) compared to ␣2-3 SAs. Our study suggested that the emergence of strains with different antigenicities was the possible reason for the increased detections of EV68 in recent years. Additionally, we revealed that EV68 preferably binds to ␣2-6 SAs. This is the first report describing the properties of EV68 receptor binding to the specific types of sialic acids.

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In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity

Cited by 185 publications

References 54 publications

Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses

Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses

Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein

Antigenic and Receptor Binding Properties of Enterovirus 68

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