#Human #infection with a novel #reassortant #Eurasian-avian lineage #swine #H1N1 virus in northern #China (Emerg Microbes Infect., abstract)

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

Emerg Microbes Infect. 2019;8(1):1535-1545. doi: 10.1080/22221751.2019.1679611.

Human infection with a novel reassortant Eurasian-avian lineage swine H1N1 virus in northern China.

Li X1, Guo L1, Liu C2, Cheng Y3, Kong M1, Yang L3, Zhuang Z1, Liu J3, Zou M1, Dong X1, Su X1, Gu Q1.

Author information: 1 Tianjin Centers for Disease Control and Prevention, Tianjin, People’s Republic of China. 2 Jizhou District Center for Disease Control and Prevention, Tianjin, People’s Republic of China. 3 Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China.

 

Abstract

Influenza A virus infections occur in different species, causing mild to severe respiratory symptoms that lead to a heavy disease burden. Eurasian avian-like swine influenza A(H1N1) viruses (EAS-H1N1) are predominant in pigs and occasionally infect humans. An influenza A(H1N1) virus was isolated from a boy who was suffering from fever and headache and designated as A/Tianjin-baodi/1606/2018(H1N1). Full-genome sequencing and phylogenetic analysis revealed that A/Tianjin-baodi/1606/2018(H1N1) is a novel reassortant EAS-H1N1 containing gene segments from EAS-H1N1 (HA and NA), classical swine H1N1(NS) and A(H1N1)pdm09(PB2, PB2, PA, NP and M) viruses. The isolation and analysis of A/Tianjin-baodi/1606/2018(H1) provide further evidence that EAS-H1N1 poses a threat to human health and greater attention should be paid to surveillance of influenza virus infection in pigs and humans.

KEYWORDS: EAS-H1N1; Influenza A virus; Phylogenetic analysis; molecular characteristics; triple-reassortant

PMID: 31661383 PMCID: PMC6830285 DOI: 10.1080/22221751.2019.1679611 [Indexed for MEDLINE] Free PMC Article

Keywords: Influenza A; Swine Influenza; H1N1; H1N1pdm09; Reassortant strain; Human; China.

——

#Serological evidence of #swine exposure to #H1N1pdm09 #influenza A virus in #Burkina Faso (Vet Microbiol., abstract)

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

Vet Microbiol. 2020 Feb;241:108572. doi: 10.1016/j.vetmic.2019.108572. Epub 2019 Dec 31.

Serological evidence of swine exposure to pandemic H1N1/2009 influenza A virus in Burkina Faso.

Tialla D1, Sausy A2, Cissé A3, Sagna T4, Ilboudo AK5, Ouédraogo GA6, Hübschen JM7, Tarnagda Z8, Snoeck CJ9.

Author information: 1 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso; Ecole Nationale de l’Elevage et de la Santé Animale (ENESA), Secteur 28, Ouagadougou, Burkina Faso. Electronic address: tialladfaso@yahoo.fr. 2 Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address: aurelie.sausy@lih.lu. 3 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: assanacisse@yahoo.fr. 4 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: stanilinda@gmail.com. 5 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: ilboudokader@yahoo.fr. 6 Laboratoire de Recherche et d’Enseignement en Santé et Biotechnologies Animales (LARESBA), Université Nazi Boni, 01 BP 109, Bobo-Dioulasso, Burkina Faso. Electronic address: ogeorgesanicet@yahoo.fr. 7 Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address: judith.huebschen@lih.lu. 8 Unité des Maladies à potentiel Epidémique, Maladies Emergentes et Zoonoses (UMEMEZ), Département Biomédical et Santé Publique, Institut de Recherche en Sciences de la Santé (IRSS), 399, Avenue de la Liberté 01, BP 545, Bobo-Dioulasso, Burkina Faso. Electronic address: zekiba@hotmail.com. 9 Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29 rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg. Electronic address: chantal.snoeck@lih.lu.

 

Abstract

Despite improvement of human and avian influenza surveillance, swine influenza surveillance in sub-Saharan Africa is scarce and pandemic preparedness is still deemed inadequate, including in Burkina Faso. This cross-sectional study therefore aimed to investigate the (past) exposure of pigs to influenza A viruses. Practices of people with occupational contacts with pigs and their knowledge on influenza A were investigated in order to formulate future prevention guidelines. In 2016-2017, pig nasopharyngeal swabs and sera were collected and screened for the presence of influenza virus by RT-PCR or of anti-influenza antibodies by competitive ELISA. Seropositive samples were further characterized in virus microneutralization assays against human and swine H1N1 virus strains. Nasopharyngeal swabs were obtained from people with occupational contact with pigs and screened similarly. Demographic data as well as practices related to their profession were recorded. No influenza A virus was detected in nasopharyngeal swabs in humans (n = 358) or in pigs (n = 600). Seroprevalence in pigs reached 6.8 % (41/600) and seropositive animals were found in 50.0 % of extensive settings (10/20) and 19.0 % of (semi-)intensive farms (4/21). All positive sera reacted against the pandemic H1N1/2009 strain, while seropositivity against two Eurasian avian-like and one American swine H1N1 strains and individual titers were lower. These results suggested exposure to pandemic H1N1/2009 virus and cross-reactivity to other H1N1 strains. Farmers with higher frequency of contact to pigs, absence of protective equipment and lack of knowledge on zoonoses are likely key players in driving human-to-swine virus transmission.

Copyright © 2020 Elsevier B.V. All rights reserved.

KEYWORDS: Burkina Faso; Epidemiology; Influenza A virus; Pandemic H1N1/2009; Pigs; Public health; Reverse zoonosis

PMID: 31928706 DOI: 10.1016/j.vetmic.2019.108572

Keywords: Influenza A; H1N1pdm09; Pigs; Burkina Faso.

——

A molecularly engineered #antiviral banana #lectin inhibits #fusion and is efficacious against #influenza virus infection in vivo (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.]

A molecularly engineered antiviral banana lectin inhibits fusion and is efficacious against influenza virus infection in vivo

Evelyn M. Covés-Datson, Steven R. King, Maureen Legendre, Auroni Gupta, Susana M. Chan, Emily Gitlin, Vikram V. Kulkarni, Jezreel Pantaleón García, Donald F. Smee, Elke Lipka, Scott E. Evans, E. Bart Tarbet, Akira Ono, and David M. Markovitz

PNAS first published January 13, 2020 / DOI: https://doi.org/10.1073/pnas.1915152117

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved December 19, 2019 (received for review September 8, 2019)

 

Significance

There is a pressing need for new antiinfluenza therapeutic agents. We show that a molecularly engineered banana lectin (carbohydrate-binding protein) has broad-spectrum activity against all influenza strains tested, including drug-resistant and currently circulating strains; is safe upon repeated administration in mice; and, moreover, is efficacious at treating lethal influenza infection via clinically pertinent routes of administration. We demonstrate that the lectin binds to the viral hemagglutinin glycoprotein and exerts its primary antiviral effect via inhibition of an early stage of the viral life cycle, viral membrane fusion to the host endosomal membrane. Our findings indicate that this engineered lectin, which has a mechanism of action quite distinct from the presently available agents, has potential as an antiinfluenza agent.

 

Abstract

There is a strong need for a new broad-spectrum antiinfluenza therapeutic, as vaccination and existing treatments are only moderately effective. We previously engineered a lectin, H84T banana lectin (H84T), to retain broad-spectrum activity against multiple influenza strains, including pandemic and avian, while largely eliminating the potentially harmful mitogenicity of the parent compound. The amino acid mutation at position 84 from histidine to threonine minimizes the mitogenicity of the wild-type lectin while maintaining antiinfluenza activity in vitro. We now report that in a lethal mouse model H84T is indeed nonmitogenic, and both early and delayed therapeutic administration of H84T intraperitoneally are highly protective, as is H84T administered subcutaneously. Mechanistically, attachment, which we anticipated to be inhibited by H84T, was only somewhat decreased by the lectin. Instead, H84T is internalized into the late endosomal/lysosomal compartment and inhibits virus–endosome fusion. These studies reveal that H84T is efficacious against influenza virus in vivo, and that the loss of mitogenicity seen previously in tissue culture is also seen in vivo, underscoring the potential utility of H84T as a broad-spectrum antiinfluenza agent.

influenza virus – hemagglutinin – membrane fusion – lectin – antiviral

Keywords: Antivirals; Banana lectin; Influenza A; Animal models.

——-

Comparative #Pathogenicity and #Transmissibility of #H1N1pdm09, #Avian #H5N1, and #Human #H7N9 #Influenza Viruses in Tree #Shrews (Front Microbiol., abstract)

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

Front Microbiol. 2019 Dec 20;10:2955. doi: 10.3389/fmicb.2019.02955. eCollection 2019.

Comparative Pathogenicity and Transmissibility of Pandemic H1N1, Avian H5N1, and Human H7N9 Influenza Viruses in Tree Shrews.

Xu S1, Li X1, Yang J1, Wang Z1, Jia Y1, Han L1, Wang L1, Zhu Q1.

Author information: 1 State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

 

Abstract

Influenza A viruses (IAVs) continuously challenge the poultry industry and human health. Studies of IAVs are still hampered by the availability of suitable animal models. Chinese tree shrews (Tupaia belangeri chinensis) are closely related to primates physiologically and genetically, which make them a potential animal model for human diseases. In this study, we comprehensively evaluated infectivity and transmissibility in Chinese tree shrews by using pandemic H1N1 (A/Sichuan/1/2009, pdmH1N1), avian-origin H5N1 (A/Chicken/Gansu/2/2012, H5N1) and early human-origin H7N9 (A/Suzhou/SZ19/2014, H7N9) IAVs. We found that these viruses replicated efficiently in primary tree shrew cells and tree shrews without prior adaption. Pathological lesions in the lungs of the infected tree shrews were severe on day 3 post-inoculation, although clinic symptoms were self-limiting. The pdmH1N1 and H7N9 viruses, but not the H5N1 virus, transmitted among tree shrews by direct contact. Interestingly, we also observed that unadapted H7N9 virus could transmit from tree shrews to naïve guinea pigs. Virus-inoculated tree shrews generated a strong humoral immune response and were protected from challenge with homologous virus. Taken together, our findings suggest the Chinese tree shrew would be a useful mammalian model to study the pathogenesis and transmission of IAVs.

Copyright © 2019 Xu, Li, Yang, Wang, Jia, Han, Wang and Zhu.

KEYWORDS: H1N1; H5N1; H7N9; infectivity; transmissibility; tree shrew

PMID: 31921093 PMCID: PMC6933948 DOI: 10.3389/fmicb.2019.02955

Keywords: Influenza A; H7N9; H5N1; H1N1pdm09; Animal models.

——

Heterologous viral protein #interactions within licensed seasonal #influenza virus #vaccines (npj Vaccines, abstract)

[Source: npj Vaccines, full page: (LINK). Abstract, edited.]

Heterologous viral protein interactions within licensed seasonal influenza virus vaccines

Marina Koroleva, Frances Batarse, Savannah Moritzky, Carole Henry, Francisco Chaves, Patrick Wilson, Florian Krammer, Katherine Richards & Andrea J. Sant

npj Vaccines volume 5, Article number: 3 (2020)

 

Abstract

Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In the studies reported here, we have examined the viral protein composition of a panel of licensed vaccines from different manufacturers and licensed in different years. Using western blotting, we found that, beyond HA proteins, there are detectable quantities of neuraminidase (NA), nucleoprotein (NP), and matrix proteins (M1) from both influenza A and influenza B viruses in the vaccines but that the composition differed by source and method of vaccine preparation. We also found that disparities in viral protein composition were associated with distinct patterns of elicited antibody specificities. Strikingly, our studies also revealed that many viral proteins contained in the vaccine form heterologous complexes. When H1 proteins were isolated by immunoprecipitation, NA (N1), M1 (M1-A), H3, and HA-B proteins were co-isolated with the H1. Further biochemical studies suggest that these interactions persist for at least 4 h at 37 °C and that the membrane/intracytoplasmic domains in the intact HA proteins are important for the intermolecular interactions detected. These studies indicate that, if such interactions persist after vaccines reach the draining lymph node, both dendritic cells and HA-specific B cells may take up multiple viral proteins simultaneously. Whether these interactions are beneficial or harmful to the developing immune response will depend on the functional potential of the elicited virus-specific CD4 T cells.

Keywords: Influenza A; Vaccines.

——

The effect of #mutations derived from mouse-adapted #H3N2 seasonal #influenza A virus to #pathogenicity and #host adaptation (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation

Eun-Ji Choi , Young Jae Lee , Jin-Moo Lee, Yeon-Jung Kim, Jang-Hoon Choi, Byeongwoo Ahn, Kisoon Kim, Myung Guk Han

___

Published: January 9, 2020 / DOI: https://doi.org/10.1371/journal.pone.0227516

 

Abstract

Elucidating the genetic basis of influenza A viruses (IAVs) is important to understand which mutations will determine the virulence and the host range of mammals. Here, seasonal H3N2 influenza was adapted in mice by serial passage and four mutants, each carrying amino acid substitutions related to mouse adaptation in either the PB2, HA, NP, or NA protein, were generated. To confirm the contribution of each gene to enhanced pathogenicity and mouse adaptation, mice were inoculated with the respective variants, and virulence, replication, histopathology, and infectivity were examined. The virus harboring HA mutations displayed increased infection efficiency and replication competence, resulting in higher mortality in mice relative to those infected with wild-type virus. By contrast, the NP D34N mutation caused rapid and widespread infection in multiple organs without presenting virulent symptoms. Additionally, the PB2 F323L mutation presented delayed but elevated replication competence in the respiratory tract, whereas the S331R mutation in NA showed no considerable effects on mouse adaptation. These results suggested that mouse-adapted changes in HA are major factors in increased pathogenicity and that mutations in NP and PB2 also contribute to cross-species adaptability. Our findings offer a better understanding of the molecular basis for IAV pathogenicity and adaptation in a new host.

___

Citation: Choi E-J, Lee YJ, Lee J-M, Kim Y-J, Choi J-H, Ahn B, et al. (2020) The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation. PLoS ONE 15(1): e0227516. https://doi.org/10.1371/journal.pone.0227516

Editor: Man-Seong Park, Korea University College of Medicine and School of Medicine, REPUBLIC OF KOREA

Received: August 7, 2019; Accepted: December 19, 2019; Published: January 9, 2020

Copyright: © 2020 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by grants of the National Institute of Health, Korea (2017-NI43001 and 2014-ER4301-02). The funder provided experiment resources, equipment, reagents and space, and helped to complete manuscript by pay the cost for English proofreading service, http://www.cdc.go.kr/index.es?sid=a5. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Influenza A; H3N2; Viral pathogenesis; Animal models.

——

#Genetic #variations on 31 and 450 residues of #influenza A #nucleoprotein affect viral #replication and translation (J Biomed Sci., abstract)

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

J Biomed Sci. 2020 Jan 6;27(1):17. doi: 10.1186/s12929-019-0612-z.

Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation.

Hung SJ1, Hsu YM1, Huang SW2, Tsai HP1,3, Lee LYY4, Hurt AC4, Barr IG4, Shih SR5, Wang JR6,7,8,9.

Author information: 1 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 701, Taiwan. 2 National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Tainan, Taiwan. 3 Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan. 4 WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia. 5 Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 6 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 701, Taiwan. jrwang@mail.ncku.edu.tw. 7 Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan. jrwang@mail.ncku.edu.tw. 8 Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan. jrwang@mail.ncku.edu.tw. 9 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan. jrwang@mail.ncku.edu.tw.

 

Abstract

BACKGROUND:

Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription.

METHODS:

To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties.

RESULTS:

The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and 450S decreased polymerase activity while the dominant residues (31 K and 450G) had higher activity. The 31 K and 450G showed better viral translation and replication in vitro and in vivo.

CONCLUSIONS:

These findings indicated variations identified in evolution have roles in modulating viral replication in vitro and in vivo. This study demonstrates that the interaction between variations of NP during virus evolution deserves future attention.

KEYWORDS: Evolution; Ferret study; H3N2; Influenza virus; Nucleoprotein; Viral replication; Viral translation

PMID: 31906961 DOI: 10.1186/s12929-019-0612-z

Keywords: Influenza A; H3N2; Viral pathogenesis.

——