#H5N8 and #H7N9 packaging signals constrain #HA #reassortment with a seasonal #H3N2 #influenza A virus (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

H5N8 and H7N9 packaging signals constrain HA reassortment with a seasonal H3N2 influenza A virus

Maria C. White, Hui Tao, John Steel, and Anice C. Lowen

PNAS published ahead of print February 13, 2019 / DOI: https://doi.org/10.1073/pnas.1818494116

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved January 17, 2019 (received for review October 26, 2018)

 

Significance

Influenza A viruses (IAV) can exchange genetic material in coinfected cells in a process termed reassortment. The last three IAV pandemic strains arose from reassortment events involving human and nonhuman IAVs. Because introduction of the hemagglutinin (HA) gene from a nonhuman virus is required for a pandemic, we addressed the compatibility of human and avian IAV. We show that sequence differences between human and avian HA genes limit the potential for reassortment. However, human IAV still incorporated heterologous HA genes at a low level in coinfected animals. This observed low level of incorporation could become significant if reassortant viruses had a fitness advantage within the host, such as resistance to preexisting immunity, and highlights the continued need for IAV surveillance.

 

Abstract

Influenza A virus (IAV) has a segmented genome, which (i) allows for exchange of gene segments in coinfected cells, termed reassortment, and (ii) necessitates a selective packaging mechanism to ensure incorporation of a complete set of segments into virus particles. Packaging signals serve as segment identifiers and enable segment-specific packaging. We have previously shown that packaging signals limit reassortment between heterologous IAV strains in a segment-dependent manner. Here, we evaluated the extent to which packaging signals prevent reassortment events that would raise concern for pandemic emergence. Specifically, we tested the compatibility of hemagglutinin (HA) packaging signals from H5N8 and H7N9 avian IAVs with a human seasonal H3N2 IAV. By evaluating reassortment outcomes, we demonstrate that HA segments carrying H5 or H7 packaging signals are significantly disfavored for incorporation into a human H3N2 virus in both cell culture and a guinea pig model. However, incorporation of the heterologous HAs was not excluded fully, and variants with heterologous HA packaging signals were detected at low levels in vivo, including in naïve contact animals. This work indicates that the likelihood of reassortment between human seasonal IAV and avian IAV is reduced by divergence in the RNA packaging signals of the HA segment. These findings offer important insight into the molecular mechanisms governing IAV emergence and inform efforts to estimate the risks posed by H7N9 and H5N8 subtype avian IAVs.

influenza A virus – reassortment – packaging – zoonosis – antigenic shift

Keywords: Influenza A; Pandemic Influenza; Seasonal Influenza; Avian Influenza; Reassortant strain; H3N2; H5N8; H7N9; Animal models.

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A Novel #Reassortant #Avian #H7N6 #Influenza Virus Is Transmissible in Guinea Pigs via Respiratory #Droplets (Front Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Front Microbiol. 2019 Jan 22;10:18. doi: 10.3389/fmicb.2019.00018. eCollection 2019.

A Novel Reassortant Avian H7N6 Influenza Virus Is Transmissible in Guinea Pigs via Respiratory Droplets.

Zhao Z1,2, Liu L1, Guo Z2, Zhang C2, Wang Z2, Wen G1, Zhang W1, Shang Y1, Zhang T1, Jiao Z1, Chen L3, Zhang C3, Cui H3, Jin M4, Wang C2, Luo Q1, Shao H1.

Author information: 1 Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan, China. 2 Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China. 3 College of Veterinary Medicine, Hebei Agricultural University, Baoding, China. 4 College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

 

Abstract

Since 2013, H7N9 and H5N6 avian influenza viruses (AIVs) have caused sporadic human infections and deaths and continued to circulate in the poultry industry. Since 2014, H7N6 viruses which might be reassortants of H7N9 and H5N6 viruses, have been isolated in China. However, the biological properties of H7N6 viruses are unknown. Here, we characterize the receptor binding preference, pathogenicity and transmissibility of a H7N6 virus A/chicken/Hubei/00095/2017(H7N6) (abbreviated HB95), and a closely related H7N9 virus, A/chicken/Hubei/00093/2017(H7N9) (abbreviated HB93), which were isolated from poultry in Hubei Province, China, in 2017. Phylogenetic analyses demonstrated that the hemagglutinin (HA) gene of HB95 is closely related to those of HB93 and human-origin H7N9 viruses, and that the neuraminidase (NA) gene of HB95 shared the highest nucleotide similarity with those of H5N6 viruses. HB95 and HB93 had binding affinity for human-like α2, 6-linked sialic acid receptors and were virulent in mice without prior adaptation. In addition, in guinea pig model, HB93 was transmissible by direct contact, but HB95 was transmissible via respiratory droplets. These results revealed the potential threat to public health posed by H7N6 influenza viruses and emphasized the need for continued surveillance of the circulation of this subtype in poultry.

KEYWORDS: avian H7N6 influenza A virus; pathogenicity; reassortment; receptor binding; transmissibility

PMID: 30723462 PMCID: PMC6349713 DOI: 10.3389/fmicb.2019.00018 Free PMC Article

Keywords: Avian Influenza; H7N9; H5N6; H7N6; Reassortant strain; Animal models.

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#Avian #H5N1 #influenza virus #infection causes severe #pneumonia in the Northern tree shrew (Tupaia belangeri) (Virology, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virology. 2019 Jan 19;529:101-110. doi: 10.1016/j.virol.2019.01.015. [Epub ahead of print]

Avian H5N1 influenza virus infection causes severe pneumonia in the Northern tree shrew (Tupaia belangeri).

Sanada T1, Yasui F2, Honda T1, Kayesh MEH3, Takano JI4, Shiogama Y4, Yasutomi Y4, Tsukiyama-Kohara K3, Kohara M5.

Author information: 1 Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. 2 Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address: yasui-fm@igakuken.or.jp. 3 Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima-city, Kagoshima 890-0065, Japan. 4 Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan. 5 Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address: kohara-mc@igakuken.or.jp.

 

Abstract

Avian-origin influenza viruses like H5N1 and H7N9 often cause severe symptoms with high mortality in humans. Animal models are useful for clarification of the mechanisms of pathogenicity of these infections. In this study, to expand the potential utility of the Northern tree shrew (Tupaia belangeri) for influenza virus infection, we assessed the pathogenicity of H5N1 and H7N9 avian influenza viruses in tupaia. Infectious virus was detected continuously from nasal, oral, tracheal, and conjunctival swab samples in the animals infected with these viruses. H5N1 influenza virus infection of tupaia caused severe diffuse pneumonia with fever and weight loss. In contrast, H7N9 influenza virus infection caused focal pneumonia. The severity of pneumonia was correlated with proinflammatory cytokine transcript levels. These results indicated that tupaia can be another suitable animal model for avian influenza virus research.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS: Avian influenza virus; H5N1; H7N9; Tree shrew; Tupaia belangeri

PMID:  30684692  DOI:  10.1016/j.virol.2019.01.015

Keywords: Avian Influenza; H5N1; H7N9; Animal models.

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#Clinical indices and #mortality of hospitalized #avian #influenza A (#H7N9) patients in #Guangdong, #China (Chin Med J (Engl.), abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Chin Med J (Engl). 2019 Feb 5;132(3):302-310. doi: 10.1097/CM9.0000000000000043.

Clinical indices and mortality of hospitalized avian influenza A (H7N9) patients in Guangdong, China.

Yang Y1, Li X1, Birkhead GS2, Zheng Z1, Lu JH1,3,4.

Author information: 1 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. 2 Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, NY 12222, USA. 3 Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong 510080, China. 4 One Health Center of Excellence for Research & Training, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.

 

Abstract

BACKGROUND:

Six epidemic waves of human infection with avian influenza A (H7N9) virus have emerged in China with high mortality. However, study on quantitative relationship between clinical indices in ill persons and H7N9 outcome (fatal and non-fatal) is still unclear. A retrospective cohort study was conducted to collect laboratory-confirmed cases with H7N9 viral infection from 2013 to 2015 in 23 hospitals across 13 cities in Guangdong Province, China.

METHODS:

Multivariable logistic regression model and classification tree model analyses were used to detect the threshold of selected clinical indices and risk factors for H7N9 death. The receiver operating characteristic curve (ROC) and analyses were used to compare survival and death distributions and differences between indices. A total of 143 cases with 90 survivors and 53 deaths were investigated.

RESULTS:

Average age (Odds Ratio (OR) = 1.036, 95% Confidence Interval (CI) = 1.016-1.057), interval days between dates of onset and confirmation (OR = 1.078, 95% CI = 1.004-1.157), interval days between onset and oseltamivir treatment (OR = 5.923, 95% CI = 1.877-18.687), body temperature (BT) (OR = 3.612, 95% CI = 1.914-6.815), white blood cell count (WBC) (OR = 1.212, 95% CI = 1.092-1.346) were significantly associated with H7N9 death after adjusting for confounders. The chance of death from H7N9 infection was 80.0% if BT was over 38.1 °C, and chance of death is 67.4% if WBC count was higher than 9.5 (10/L). Only 27.1% of patients who began oseltamivir treatment less than 9.5 days after disease onset died, compared to 68.8% of those who started treatment more than 15.5 days after onset.

CONCLUSIONS:

The intervals between date of onset and confirmation of diagnosis, between date of onset to oseltamivir treatment, age, BT and WBC are found to be the best predictors of H7N9 mortality.

PMID: 30681496 DOI: 10.1097/CM9.0000000000000043

Keywords: Avian Influenza; H7N9; Human; China; Guangdong.

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#Generation of #H7N9-specific #human polyclonal #antibodies from a transchromosomic #goat (caprine) system (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Jan 23;9(1):366. doi: 10.1038/s41598-018-36961-5.

Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system.

Wu H1,2, Fan Z3, Brandsrud M1, Meng Q3, Bobbitt M1, Regouski M3, Stott R3, Sweat A3, Crabtree J4, Hogan RJ4, Tripp RA4, Wang Z5, Polejaeva IA6, Sullivan EJ7,8.

Author information: 1 SAB Biotherapeutics, Sioux Falls, SD, 57104, USA. 2 SAB Capra, LLC, Salt Lake City, UT, 84101, USA. 3 Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322, USA. 4 Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA. 5 Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322, USA. zonda.wang@usu.edu. 6 Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, 84322, USA. irina.polejaeva@usu.edu. 7 SAB Biotherapeutics, Sioux Falls, SD, 57104, USA. esullivan@sabbiotherapeutics.com. 8 SAB Capra, LLC, Salt Lake City, UT, 84101, USA. esullivan@sabbiotherapeutics.com.

 

Abstract

To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat. We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production. Gene and protein expression analyses in the peripheral blood mononuclear cells (PBMC) and the sera, respectively, of Tc caprine demonstrated the successful expression of human Ig genes and antibodies. Furthermore, immunization of Tc caprine with inactivated influenza A (H7N9) viruses followed by H7N9 Hemagglutinin 1 (HA1) boosting elicited human antibodies with high neutralizing activities against H7N9 viruses in vitro. As a small ungulate, Tc caprine offers the advantages of low cost and quick establishment of herds, therefore complementing the Tc cattle platform in responses to a range of medical needs and diagnostic applications where small volumes of human antibody products are needed.

PMID: 30675003 DOI: 10.1038/s41598-018-36961-5

Keywords: Avian Influenza; H7N9; Serotherapy.

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Characterization of a novel #reassortant #H7N3 highly pathogenic #avian #influenza virus isolated from a #poultry #meat product taken on a passenger flight to #Japan (J Vet Med Sci., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Vet Med Sci. 2019 Jan 24. doi: 10.1292/jvms.18-0628. [Epub ahead of print]

Characterization of a novel reassortant H7N3 highly pathogenic avian influenza virus isolated from a poultry meat product taken on a passenger flight to Japan.

Shibata A1, Harada R1, Okamatsu M2, Matsuno K2,3, Arita T4, Suzuki Y4, Shirakura M4, Odagiri T4, Takemae N5, Uchida Y5, Saito T5, Sakoda Y2,3, Osaka H1.

Author information: 1 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries. 2 Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University. 3 Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University. 4 Influenza Virus Research Center, National Institute of Infectious Diseases. 5 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO).

 

Abstract

A new reassortant H7N3 avian influenza virus (AIV) was isolated from a duck meat product that was illegally taken on board a passenger flight from China to Japan in March 2018. Sequencing analysis revealed that the H7N3 isolate, A/duck/Japan/AQ-HE30-1/2018 (Dk/HE30-1) (H7N3), was a reassortant highly pathogenic avian influenza virus (HPAIV) that contained the haemagglutinin (HA) gene of Chinese H7N9 HPAIV. Dk/HE30-1 (H7N3) possessed a novel polybasic sequence motif PEVPKRRRTAR/GLF at the HA cleavage site that has never previously been reported in H7 HPAIVs. The HA antigenicity of Dk/HE30-1 (H7N3) slightly differed from that of H7N9 HPAIVs previously reported. These findings will help further our knowledge of the circulation and genetic evolution of emerging AIVs in endemic areas.

KEYWORDS: H7N3 subtype; highly pathogenic avian influenza virus; reassortant virus

PMID: 30674734 DOI: 10.1292/jvms.18-0628

Keywords: Avian Influenza; H7N3; H7N9; Reassortant strain; Poultry; Japan; China.

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Recombinant #baculovirus #vaccine expressing hemagglutinin of #H7N9 #avian #influenza virus confers full protection against lethal highly pathogenic H7N9 virus infection in #chickens (Arch Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Arch Virol. 2019 Jan 22. doi: 10.1007/s00705-018-04142-4. [Epub ahead of print]

Recombinant baculovirus vaccine expressing hemagglutinin of H7N9 avian influenza virus confers full protection against lethal highly pathogenic H7N9 virus infection in chickens.

Hu J1,2,3, Liang Y1,2,3, Hu Z1,2,3, Wang X1,2,3, Gu M1,2,3, Li R1,2,3, Ma C1,2,3, Liu X1,2,3, Hu S1,2,3, Chen S1,2,3, Peng D1,2,3, Jiao X2,4,3, Liu X5,6,7.

Author information: 1 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, Jiangsu, 225009, China. 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China. 3 Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. 4 Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China. 5 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, Jiangsu, 225009, China. xfliu@yzu.edu.cn. 6 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China. xfliu@yzu.edu.cn. 7 Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China. xfliu@yzu.edu.cn.

 

Abstract

The emergent highly pathogenic avian influenza A (H7N9) (HPAI) virus is a major public concern in China. Therefore, it is crucially important to develop an effective vaccine against this virus. In this study, we constructed a baculovirus vaccine expressing the hemagglutinin (HA) of H7N9 strain A/Chicken/Jiaxing/148/2014 (JX148). The recombinant baculovirus (rBac-JX148HA) generated in this study showed good growth in insect cells and good safety, and it stably expressed the HA protein. We compared the immunogenicity and efficacy of the inactivated whole-virus vaccine JX148 and rBac-JX148HA. One chicken in the JX148-treated group died on day 4 post-challenge, and three chickens had typical clinical symptoms (survival rate, 90%; morbidity, 40%). However, no chickens immunized with rBac-JX148HA showed clinical signs during the 14-day observation period. An analysis of viral shedding and viral replication demonstrated that rBac-JX148HA more efficiently inhibited viral shedding and viral replication than the inactivated whole-virus vaccine. Taken together, these results indicate that the inactivated recombinant baculovirus vaccine induces a high hemagglutination inhibition antibody titer, provides complete protection against challenge with the highly pathogenic H7N9 virus, and effectively inhibits viral shedding. Therefore, the candidate vaccine has potential utility in the prevention and control of H7N9 avian influenza and is also appropriate for veterinary vaccines using cell suspension culture technology.

PMID: 30671655 DOI: 10.1007/s00705-018-04142-4

Keywords: Avian Influenza; H7N9; Poultry; Vaccines; China.

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