Successful #Treatment With #Baloxavir Marboxil of a Patient With #Peramivir #Resistant #Influenza A / #H3N2 With a Dual E119D/R292K Substitution After Allogeneic Hematopoietic Cell #Transplantation: A Case Report (BMC Infect Dis., abstract)

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

BMC Infect Dis. 2020 Jul 6;20(1):478. doi: 10.1186/s12879-020-05205-1.

Successful Treatment With Baloxavir Marboxil of a Patient With Peramivir-Resistant Influenza A/H3N2 With a Dual E119D/R292K Substitution After Allogeneic Hematopoietic Cell Transplantation: A Case Report

Naonori Harada 1, Wataru Shibata 2 3, Hideo Koh 4, Emi Takashita 5, Seiichiro Fujisaki 5, Hiroshi Okamura 1, Satoru Nanno 1, Koichi Yamada 2 3, Hirohisa Nakamae 1, Masayuki Hino 1, Hiroshi Kakeya 2 3

Affiliations: 1 Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. 2 Department of Infection Control Science, Graduate School of Medicine, Osaka City University, Osaka, Japan. 3 Research Center for Infectious Disease Sciences (RCIDS), Graduate School of Medicine, Osaka City University, Osaka, Japan. 4 Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. 5 Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

PMID: 32631240 DOI: 10.1186/s12879-020-05205-1




Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir.

Case presentation:

A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/μL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2.


In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.

Keywords: Allogeneic hematopoietic cell transplantation; Baloxavir marboxil; Dual E119D/R292K substitution; Immunocompromised host; Influenza A/H3N2; Neuraminidase mutation; Peramivir resistance.

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Hematology; H3N2; Cancer; Immunosuppression; Peramivir; Baloxavir.


#Neuraminidase #antigenic #drift of #H3N2 clade 3c.2a viruses alters virus #replication, enzymatic activity and inhibitory #antibody binding (PLOS Pathog., abstract)

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


Neuraminidase antigenic drift of H3N2 clade 3c.2a viruses alters virus replication, enzymatic activity and inhibitory antibody binding

Harrison Powell, Andrew Pekosz

Published: June 29, 2020 | DOI: | This is an uncorrected proof.



In the 2014–2015 influenza season a novel neuraminidase (NA) genotype was detected in global human influenza A surveillance. This novel genotype encoded an N-linked glycosylation site at position 245–247 in the NA protein from clade 3c.2a H3N2 viruses. In the years following the 2014–2015 season, this novel NA glycosylation genotype quickly dominated the human H3N2 population of viruses. To assess the effect this novel N-linked glycan has on virus fitness and antibody binding, recombinant viruses with (NA Gly+) or without (NA Gly-) the 245 NA glycan were created. Viruses with the 245 NA Gly+ genotype grew to a significantly lower infectious virus titer on primary, differentiated human nasal epithelial cells (hNEC) compared to viruses with the 245 NA Gly- genotype, but growth was similar on immortalized cells. The 245 NA Gly+ blocked human and rabbit monoclonal antibodies that target the enzymatic site from binding to their epitope. Additionally, viruses with the 245 NA Gly+ genotype had significantly lower enzymatic activity compared to viruses with the 245 NA Gly- genotype. Human monoclonal antibodies that target residues near the 245 NA glycan were less effective at inhibiting NA enzymatic activity and virus replication of viruses encoding an NA Gly+ protein compared to ones encoding NA Gly- protein. Additionally, a recombinant H6N2 virus with the 245 NA Gly+ protein was more resistant to enzymatic inhibition from convalescent serum from H3N2-infected humans compared to viruses with the 245 NA Gly- genotype. Finally, the 245 NA Gly+ protected from NA antibody mediated virus neutralization. These results suggest that while the 245 NA Gly+ decreases virus replication in hNECs and decreases enzymatic activity, the 245 NA glycan blocks the binding of monoclonal and human serum NA specific antibodies that would otherwise inhibit enzymatic activity and virus replication.


Author summary

Influenza virus infects millions of people worldwide and leads to thousands of deaths and millions in economic loss each year. During the 2014/2015 season circulating human H3N2 viruses acquired a novel mutation in the neuraminidase (NA) protein. This mutation has since fixed in human H3N2 viruses. This mutation at position 245 through 247 in the amino acid sequence of NA encoded an N-linked glycosylation. Here, we studied how this N-linked glycan impacts virus fitness and protein function. We found that this N-linked glycan on the NA protein decreased viral replication fitness on human nasal epithelial cells (hNEC) but not immortalized Madin-Darby Canine Kidney (MDCK) cells. We also determined this glycan decreases NA enzymatic activity, enzyme kinetics and affinity for substrate. Furthermore, we show that this N-linked glycan at position 245 blocks some NA specific inhibitory antibodies from binding to the protein, inhibiting enzymatic activity, and inhibiting viral replication. Finally, we showed that viruses with the novel 245 N-linked glycan are more resistant to convalescent human serum antibody mediated enzymatic inhibition. While this 245 N-linked Glycan decreases viral replication and enzymatic activity, the 245 N-linked glycan protects the virus from certain NA specific inhibitory antibodies. Our study provides new insight into the function of this dominant H3N2 NA mutation and how it impacts antigenicity and fitness of circulating H3N2 viruses.


Citation: Powell H, Pekosz A (2020) Neuraminidase antigenic drift of H3N2 clade 3c.2a viruses alters virus replication, enzymatic activity and inhibitory antibody binding. PLoS Pathog 16(6): e1008411.

Editor: Anice C. Lowen, Emory University School of Medicine, UNITED STATES

Received: February 13, 2020; Accepted: May 11, 2020; Published: June 29, 2020

Copyright: © 2020 Powell, Pekosz. 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.

Funding: The work was supported by CEIRS HHSN272201400007C and T32 AI007417 (HP). The funders 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: Seasonal Influenza; Influenza A; H3N2; Viral pathogenesis.


#Aerosol #transmission from infected #swine to #ferrets of an #H3N2 virus collected from an #agricultural #fair and associated with #human variant infections (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Aerosol transmission from infected swine to ferrets of an H3N2 virus collected from an agricultural fair and associated with human variant infections

Bryan S. Kaplan, J. Brian Kimble, Jennifer Chang, Tavis K. Anderson, Phillip C. Gauger, Alicia Janas-Martindale, Mary Lea Killian, Andrew S. Bowman, Amy L. Vincent

DOI: 10.1128/JVI.01009-20



Influenza A viruses (IAV) sporadically transmit from swine to humans, typically associated with agricultural fairs in the USA. A human seasonal H3 from the 2010-2011 IAV season was introduced into the US swine population and termed H3.2010.1 to differentiate from the previous swine H3. This H3N2 lineage became widespread in the US commercial swine population, subsequently spilling over into exhibition swine, and caused a majority of H3N2 variant (H3N2v) cases in humans in 2016 and 2017. A cluster of human H3N2v cases were reported at an agricultural fair in Ohio in 2017 where 2010.1 H3N2 IAV was concurrently detected in exhibition swine. Genomic analysis showed the swine and human isolates were nearly identical. Here we evaluated the propensity of a 2010.1 H3N2 IAV (A/swine/Ohio/A01354299/2017; sw/OH/2017) isolated from a pig in the agricultural fair outbreak to replicate in ferrets and transmit from swine to ferret. Sw/OH/2017 displayed robust replication in the ferret respiratory tract, causing slight fever and moderate weight loss. Further, sw/OH/2017 was capable of efficient respiratory droplet transmission from infected pigs to contact ferrets. These findings establish a model for evaluating the propensity of swine IAV to transmit from pig-to-ferret as a measure of risk to the human population. The identification of higher risk swine strains can then be targeted for control measures to limit the dissemination at human-swine interfaces to reduce the risk of zoonotic infections and inform pandemic planning.



A recently emerged lineage of human-like H3N2 (H3.2010.1) influenza A virus (IAV) from swine have been frequently detected in commercial and exhibition swine in recent years and were associated with H3N2 variant cases in humans from 2016 and 2017. To demonstrate a model for characterizing the potential for zoonotic transmission associated with swine IAV, we performed an in vivo transmission study between pigs infected with an H3.2010.1 H3N2 and aerosol contact ferrets. The efficient interspecies transmission demonstrated for the H3.2010.1 IAV-S emphasizes the need for further characterization of viruses circulating at the swine-human interface for transmission potential prior to human spillover and the development and implementation of more robust vaccines and control strategies to mitigate human exposure to higher risk swine strains.

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Keywords: Swine Influenza; Influenza A; H3N2; Reassortant strain; Pigs; Human; USA; Animal models.


#Severe cases of seasonal #influenza and detection of seasonal A(#H1N2) in #Russia in 2018–2019 (Arch Virol., abstract)

[Source: Archives of Virology, full page: (LINK). Abstract, edited.]

Severe cases of seasonal influenza and detection of seasonal A(H1N2) in Russia in 2018–2019

Natalia P. Kolosova, Tatyana N. Ilyicheva, Alexey V. Danilenko, Svetlana V. Svyatchenko, Natalia I. Goncharova, Julia A. Bulanovich, Polina Yu Torzhkova, Alexander G. Durymanov, Andrei S. Gudymo, Alexander N. Shvalov, Ivan M. Susloparov, Tatyana V. Tregubchak, Elena V. Gavrilova, Rinat A. Maksyutov & Alexander B. Ryzhikov

Archives of Virology (2020)



Data obtained from monitoring cases of severe influenza, cases of vaccinated individuals, and unique cases were used to describe influenza viruses that circulated in Russia in the 2018–2019 epidemic season. A high proportion of the mutations D222G/N in A(H1N1)pdm09 HA was detected in fatal cases. Viruses of the B/Victoria lineage with deletions in HA were detected in Russia, and a reassortant seasonal influenza A(H1N2) virus was identified. A C-terminal truncation in the NS1 protein was detected in a substantial proportion of A(H3N2) viruses.

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; H1N2; Reassortant strain; Russia.


Early #treatment with #baloxavir marboxil in high-risk #adolescent and #adult outpatients with uncomplicated #influenza (#CAPSTONE2)… (Lancet Infect Dis., abstract)

[Source: Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial

Prof Michael G Ison, MD,  Simon Portsmouth, MD, Yuki Yoshida, MS, Takao Shishido, PhD, Melissa Mitchener, PharmD, Kenji Tsuchiya, MS, Takeki Uehara, PhD, Frederick G Hayden

Published: June 08, 2020 | DOI:




Baloxavir marboxil (hereafter baloxavir), a selective inhibitor of influenza cap-dependent endonuclease, was approved in 2018 in the USA and Japan for the treatment of uncomplicated influenza in otherwise healthy individuals aged 12 years and older. We aimed to study the efficacy of baloxavir in outpatients at high risk of developing influenza-associated complications.


We did a double-blind, placebo-controlled and oseltamivir-controlled trial in outpatients aged 12 years and older in 551 sites in 17 countries and territories. Eligible patients had clinically diagnosed influenza-like illness, at least one risk factor for influenza-associated complications (eg, age older than 65 years), and a symptom duration of less than 48 h. Patients were stratified by baseline symptom score (≤14 vs ≥15), pre-existing and worsened symptoms at onset of illness compared with pre-influenza (yes or no), region (Asia, North America and Europe, or southern hemisphere), and weight (<80 kg vs ≥80 kg), and randomly assigned (1:1:1) via an interactive web-response system to either a single weight-based dose of baloxavir (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg; baloxavir group), oseltamivir 75 mg twice daily for 5 days (oseltamivir group), or matching placebo (placebo group). All patients, investigators, study personnel, and data analysts were masked to treatment assignment until database lock. The primary endpoint was time to improvement of influenza symptoms (TTIIS) in the modified intention-to-treat population, which included all patients who received at least one dose of study drug and had RT-PCR-confirmed influenza virus infection. Safety was assessed in all patients who receved at least one dose of study drug. This trial is registered with, NCT02949011.


2184 patients were enrolled from Jan 11, 2017, to March 30, 2018, and randomly assigned to receive baloxavir (n=730), placebo (n=729), or oseltamivir (n=725). The modified intention-to-treat population included 1163 patients: 388 in the baloxavir group, 386 in the placebo group, and 389 in the oseltamivir group. 557 (48%) of 1163 patients had influenza A H3N2, 484 (42%) had influenza B, 80 (7%) had influenza A H1N1, 14 patients had a mixed infection, and 28 had infections with non-typable viruses. The median TTIIS was shorter in the baloxavir group (73·2 h [95% CI 67·2 to 85·1]) than in the placebo group (102·3 h [92·7 to 113·1]; difference 29·1 h [95% CI 14·6 to 42·8]; p<0·0001). The median TTIIS in the oseltamivir group was 81·0 h (95% CI 69·4 to 91·5), with a difference from the baloxavir group of 7·7 h (−7·9 to 22·7). Adverse events were reported in 183 (25%) of 730 patients in the baloxavir group, 216 (30%) of 727 in the placebo group, and 202 (28%) of 721 in the oseltamivir group. Serious adverse events were noted in five patients in the baloxavir group, nine patients in the placebo group, and eight patients in the oseltamivir group; one case each of hypertension and nausea in the placebo group and two cases of transaminase elevation in the oseltamivir group were considered to be treatment related. Polymerase acidic protein variants with Ile38Thr, Ile38Met, or Ile38Asn substitutions conferring reduced baloxavir susceptibility emerged in 15 (5%) of 290 baloxavir recipients assessed for amino acid substitutions in the virus.


Single-dose baloxavir has superior efficacy to placebo and similar efficacy to oseltamivir for ameliorating influenza symptoms in high-risk outpatients. The safety of baloxavir was comparable to placebo. This study supports early therapy for patients at high risk of complications of influenza to speed clinical recovery and reduce complications.



Keywords: Seasonal Influenza; Antivirals; Baloxavir.


#Influenza A #H1N1pdm09 but not A #H3N2 virus #infection induces durable #seroprotection: results from the Ha Nam Cohort (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Influenza A(H1N1)pdm09 but not A(H3N2) virus infection induces durable sero-protection: results from the Ha Nam Cohort

Le Nguyen Minh Hoa, Sheena G Sullivan, Le Quynh Mai, Arseniy Khvorov, Hoang Vu Mai Phuong, Nguyen Le Khanh Hang, Pham Quang Thai, Le Thi Thanh, Louise Carolan, Dang Duc Anh, Tran Nhu Duong, Juliet E Bryant, H Rogier van Doorn, Heiman F L Wertheim, Peter Horby, Annette Fox

The Journal of Infectious Diseases, jiaa293,

Published: 02 June 2020




The extent to which influenza recurrence depends upon waning immunity from prior-infection is undefined. We used antibody titres of Ha-Nam cohort participants to estimate protection curves and decay trajectories.


270 households participated in influenza-like-illness surveillance and provided blood at intervals spanning RTPCR-confirmed transmission. Sera were tested in haemagglutination inhibition assay. Infection was defined as RTPCR+ influenza-like-illness and/or seroconversion. Median protective titres were estimated using scaled-logistic-regression to model pre-transmission titre against infection status in that season, limiting analysis to households with infection(s). Titres were modelled against month since infection using mixed-effects linear regression to estimate decay and when titres fell below protection-thresholds.


295 and 314 participants were infected with H1N1pdm09-like and A/Perth/16/09-like (H3N2Pe09) viruses, respectively between December 2008-2012. The proportion of householders not-infected (protected) rose more steeply with titre for H1N1pdm09 than for H3N2Pe09, and estimated 50% protection titres were 19.6 and 37.3, respectively. Post-infection titres started higher against H3N2Pe09 but decayed more steeply than against H1N1pdm09. Sero-protection was estimated to be sustained against H1N1pdm09 but to wane by 8-months for H3N2Pe09.


Estimates indicate that infection induces durable sero-protection against H1N1pdm09 but not H3N2Pe09, which could in part account for the younger age of A(H1N1) versus A(H3N2) cases.

Influenza A virus, antibody, immunity, H1N1 subtype, H3N2 subtype, Cohort Studies

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Immunology.


#Truncation of #PA-X contributes to #virulence and #transmission of #H3N8 and #H3N2 #canine #influenza viruses in #dogs (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Truncation of PA-X contributes to virulence and transmission of H3N8 and H3N2 canine influenza viruses in dogs

Litao Liu, Shikai Song, Ye Shen, Chao Ma, Tong Wang, Qi Tong, Honglei Sun, Juan Pu, Munir Iqbal, Jinhua Liu, Yipeng Sun

DOI: 10.1128/JVI.00949-20



Equine-origin H3N8 and avian-origin H3N2 canine influenza viruses (CIVs) prevalent in dogs are thought to pose a public health threat arising from intimate contact between dogs and humans. However, our understanding of CIV virulence is still limited. Influenza A virus PA-X is a fusion protein encoded in part by a +1 frameshifted open reading frame (X-ORF) in segment 3. The X-ORF can be translated in full-length (61 amino acids) or truncated (41 amino acids) form. Genetic analysis indicated that the X-ORFs of equine H3N8 and avian H3N2 influenza viruses encoded 61 amino acids but were truncated after introduction into dogs. To determine the effect of PA-X truncation on the biological characteristics of CIVs, we constructed four recombinant viruses on H3N8 and H3N2 CIV backgrounds bearing truncated or full-length PA-Xs. We observed that truncation of PA-X increased growth of both H3N8 and H3N2 CIVs in MDCK cells and suppressed expression from co-transfected plasmids in MDCK cells. Furthermore, truncation of PA-X enhanced viral pathogenicity in dogs as shown by aggravated clinical symptoms and histopathological changes, increased viral replication in the respiratory system, and prolonged virus shedding. Additionally, CIVs with truncated PA-Xs were transmitted more efficiently in dogs. Global gene expression profiling of the lungs of infected dogs revealed that differentially expressed genes were mainly associated with inflammatory responses, which might contribute to the pathogenicity of PA-X-truncated CIVs. Our findings revealed that truncation of PA-X might be important for the adaptation of influenza viruses to dogs.



Epidemics of equine-origin H3N8 and avian-origin H3N2 influenza viruses in canine populations are examples of successful cross-species transmission of influenza A viruses. Genetic analysis showed that the PA-X genes of equine H3N8 or avian H3N2 influenza viruses were full-length, with X-ORFs encoding 61 amino acids; however, those of equine-origin H3N8 or avian-origin H3N2 CIVs were truncated, suggesting PA-X truncation occurred after transmission to dogs. Here, we extended the PA-X genes of H3N8 and H3N2 CIVs and compared the biological characteristics of CIVs bearing different lengths of PA-X. We demonstrated that for both H3N8 and H3N2 viruses, truncation of PA-X increased virus yields in MDCK cells and enhanced viral replication, pathogenicity and transmission in dogs. These results might reflect enhanced suppression of host gene expression and up-regulation of genes related to inflammatory responses. Collectively, our data partially explain the conservation of truncated PA-X in CIVs.

Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords: Canine Avian Influenza; Influenza A; H3N2; H3N8; Dogs; Viral pathogenesis.


#Molecular #Epidemiology and #Vaccine #Compatibility #Analysis of Seasonal #Influenza Viruses in #Wuhan, 2016–2019 (Virol Sin., abstract)

[Source: Virologica Sinica, full page: (LINK). Abstract, edited.]

Molecular Epidemiology and Vaccine Compatibility Analysis of Seasonal Influenza Viruses in Wuhan, 2016–2019

Liang-Jun Chen, Jing-Jing Guo, Wei-Wei Guo, E-Xiang Shen, Xin Wang, Kai-Ji Li, Jie Yan, Mang Shi, Yi-Rong Li & Wei Hou

Virologica Sinica (2020)



Influenza viruses (FLUV) cause high morbidity and mortality annually in the world and pose a serious threat to the public health. Wuhan, as an important transportation hub in China, has a dense population and suitable climate, which also lays a major hidden danger for the outbreak of influenza. To survey and characterize the seasonal FLUV in Wuhan during 2016–2019, we collected 44,738 throat swabs, among which 15.5% were influenza A (FLUAV) positive, 6.1% influenza B (FLUBV) and 0.3% co-infection. By monitoring FLUV in each month from June 2016 to May 2019, different with the previously seasonality pattern, only a single influenza peak was appeared in winter of 2017–2018 and 2018–2019, respectively. These data indicated that the complex circulation pattern of seasonal influenza in Wuhan. In addition, we found the age group was skewed towards 5–14 years group whose activity were mostly school based, which suggested school may be an important place for influenza outbreaks. Meanwhile, phylogenic analysis revealed that two subtypes (subclade 3C.2a2 and 3C.2a1b) of A(H3N2) were circulating in Wuhan and there was an obvious transition in 2018 because the two subclades were detected simultaneously. Furthermore, by estimating the vaccine effectiveness, we found that the vaccine strain of FLUAV didn’t seem to match very well the current epidemic strain, especially A(H3N2). Hence, more accurate prediction of seasonal outbreak is essential for vaccine design. Taken together, our results provided the current information about seasonal FLUV in Wuhan which form the basis for vaccine updating.

Keywords: Seasonal Influenza; H3N2; Vaccines; China; Hubei.


Continuous #adaptation of the #HA and #NA gene of #H3N2 subtypes of #avian #influenza virus in South #China, 2017–2018 (J Infect., abstract)

[Source: Journal of Infection, full page: (LINK). Abstract, edited.]

Continuous adaptation of the HA and NA gene of H3N2 subtypes of avian influenza virus in South China, 2017–2018

Jingkai Hu, Yunfeng Zha, Xuanjiang Jin, Xiaohui Wen, Zhixian Li, Xiao Wang, Yixue Dai, Xiao Li, Ming Liao, Weixin Jia

Published: January 30, 2019 | DOI:


Recently, we read with interest a letter in the  Journal of Infection, which confirmed  avian influenza viruses has posed a new challenge for public health. 1 The H3N2 subtype  influenza virus has resulted in global pandemics since 1968, 2 and H3 has a  wide host range from birds to various mammalian species, including humans, pigs, dogs,  and horses. 3 , 4  Previous studies have shown that avian influenza viruses (AIVs)  such as H5N1 and H7N9 could adapt to mammals and gain the ability to infect humans.  Song reported cross-species transmission of an intact avian influenza virus (H3N2) to  dogs in South Korea that caused acute respiratory disease. 5  In addition, seasonal  influenza viruses of strain H3N2 have circulated in the human population every year,  and sequence analysis has shown that the novel H3N2 contains genes from H7N3 and  H7N7 that viruses are closely related to the H7N9 virus, suggesting that reassortment  occurred between H3N2 and other influenza virus subtypes. 6 Thus, evolution of H3N2 AIVs was demonstrated in this study.

Keywords: Avian Influenza; Canine Avian Influenza; Seasonal Influenza; Reassortant strain; H3N2; H7N3; H7N7; H7N9; China.


#Genetic characterization of #influenza A viruses in #Japanese #swine during 2015–2019 (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Genetic characterization of influenza A viruses in Japanese swine during 2015–2019

Junki Mine, Yuko Uchida, Nobuhiro Takemae, Takehiko Saito

DOI: 10.1128/JVI.02169-19



To assess the current status of influenza A viruses of swine (IAVs-S) throughout Japan and to investigate how these viruses persisted and evolve on pig farms, we genetically characterized IAVs-S isolated during 2015–2019. Nasal swab samples collected through active surveillance and lung tissue samples collected for diagnosis yielded 424 IAVs-S—comprising 78 H1N1, 331 H1N2, and 15 H3N2 viruses—from farms in sampled 21 prefectures in Japan. Phylogenetic analyses of surface genes revealed that the 1A.1 classical swine H1 lineage has evolved uniquely since the late 1970s among pig populations in Japan. During 2015–2019, A(H1N1)pdm09 viruses repeatedly become introduced into farms and reassorted with endemic H1N2 and H3N2 IAVs-S. H3N2 IAVs-S isolated during 2015–2019 formed a clade that originated from 1999–2000 human seasonal influenza viruses; this situation differs from previous reports, in which H3N2 IAVs-S derived from human seasonal influenza viruses were transmitted sporadically from humans to swine but then disappeared without becoming established within the pig population. At farms where IAVs-S were frequently isolated for at least 3 years, multiple introductions of IAVs-S with phylogenetically distinct HA genes occurred. In addition, at one farm, IAVs-S derived from a single introduction persisted for at least 3 years and carried no mutations at the deduced antigenic sites of the hemagglutinin protein except only one at the antigenic site (Sa). Our results extend our understanding regarding the status of IAVs-S currently circulating in Japan and how they genetically evolve at the farm level.



Understanding the current status of influenza A viruses of swine (IAVs-S) and their evolution at the farm level is important for controlling these pathogens. Efforts to monitor IAVs-S during 2015–2019 yielded H1N1, H1N2, and H3N2 viruses. H1 genes in Japanese swine formed unique clade in the classical swine H1 lineage of 1A.1, and H3 genes originating from 1999–2000 human seasonal influenza viruses appear to have become established among Japanese swine. A(H1N1)pdm09-derived H1 genes became introduced repeatedly and reassorted with endemic IAVs-S, resulting in various combinations of surface and internal genes among pig populations in Japan. At the farm level, multiple introductions of IAVs-S with phylogenetically distinct HA sequences occurred, or IAVs-S derived from a single introduction have persisted for at least 3 years with only a single mutation at the antigenic site of the HA protein. Continued monitoring of IAVs-S is necessary to update and maximize control strategies.

Copyright © 2020 Mine et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Influenza A; H1N1pdm09; H1N2; H3N2; Swine Influenza; Reassortant strain; Pigs; Japan.