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

  • ️Fri Jan 01 2016

. 2016 Jan 12;113(2):392-7.

doi: 10.1073/pnas.1522643113. Epub 2015 Dec 28.

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

Huanliang Yang et al. Proc Natl Acad Sci U S A. 2016.

Abstract

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.

Keywords: Eurasian lineage; H1N1; evolution; pandemic potential; swine influenza.

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Conflict of interest statement

Conflict of interest statement: Y.K. has received speaker’s honoraria from Toyama Chemical and Astellas Inc.; has received grant support from Chugai Pharmaceuticals, Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., and Otsuka Pharmaceutical Co., Ltd; and is a founder of FluGen.

Figures

Fig. 1.
Fig. 1.

Genetic relationships among the HA genes and genotype evolution of EAH1N1 SIVs. (A) Phylogenetic tree of HA. The unrooted tree was based on nucleotides 33–1733. Sequences of viruses with names in black were downloaded from available databases; viruses with names in colors were sequenced in this study. Scale bar indicates the number of nucleotide substitutions per site. (B) Genotypes of the EAH1N1 SIVs. The eight gene segments are indicated at the top of each bar. The colors of the bars represent the groups in the trees of Fig. 1A and SI Appendix, Fig. S2. Viruses shown in red were selected for all other tests.

Fig. 2.
Fig. 2.

Replication of EAH1N1 SIVs in ferrets. Ferrets (n = 2 per group) were inoculated i.n. with 106.0 EID50 of each virus, and the indicated organs from each ferret were collected on day 4 p.i. for virus titration in eggs. Each color bar represents the virus titer from an individual animal. The dashed blue lines indicate the lower limit of detection. (A) SW/HuN/26/10, (B) SW/GX/18/11, (C) SW/HeN/232/11, (D) SW/HLJ/27/12, (E) SW/JS/49/12, (F) SW/HuN/30/13, (G) SW/TJ/47/11, (H) SW/GD/30/13, (I) SW/GD/104/13, and (J) SW/GD/306/13.

Fig. 3.
Fig. 3.

Lung lesions caused by EAH1N1 SIVs in ferrets. Macroscopic lesions in the lungs and focal consolidations in dark red were observed in the lobes of ferrets inoculated with all of the EAH1N1 viruses (A; the image is from an SW/HuN/30/13-inoculated ferret), except for SW/GD/104/13, which did not cause obvious macroscopic lesions in the lungs of ferrets (B). Only mild histopathological changes were observed in the lungs of SW/GD/104/13-inoculated ferrets (C) (H&E staining), and viral antigen was not detected (D) (immunohistochemical staining), whereas the lungs of ferrets inoculated with SW/HuN/26/10, SW/GX/18/11, SW/HeN/232/11, SW/HLJ/27/12, SW/JS/49/12, SW/HuN/30/13, SW/TJ/47/11, SW/GD/30/13, and SW/GD/306/13 viruses showed severe pathological lesions (E–M) (H&E staining). Viral antigen was detected in the epithelial cells of the bronchus and alveoli by means of immunohistochemical staining (N, from the lung sample of a ferret inoculated with SW/HuN/30/13 virus). Images C and E–M were taken at 100× magnification; images D and N were taken at 400× magnification.

Fig. 4.
Fig. 4.

Respiratory droplet transmission of EAH1N1 SIVs in ferrets. Each line represents the virus titer from an individual animal. The dashed lines indicate the values from the inoculated animals; the solid lines indicate the values from the exposed animals. The dashed black lines indicate the lower limit of detection. (A) SW/HuN/26/10, (B) SW/GX/18/11, (C) SW/HeN/232/11, (D) SW/HLJ/27/12, (E) SW/JS/49/12, (F) SW/HuN/30/13, (G) SW/TJ/47/11, (H) SW/GD/30/13, (I) SW/GD/104/13, (J) SW/GD/306/13, and (K) SC/1/09.

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