Human Influenza Viruses Research Articles

Inhibition of the Antigen-Presenting Ability of Dendritic Cells Bynon-Structural Protein 2 of Influenza A Virus

Influenza A viruses (IAV), including human IAV and avian IAV (H9N2 subtype), are responsible for recurring influenza outbreaks worldwide in a wide range of mammalian and avian species. Dendritic cells (DCs) are specialised antigen presenting cells. However, while DCs can take up IAV and transmit it to other cells. DCs do not effectively present IAV antigens. It remains unclear why. We found that IAV Non-structural protein 2 (NS2) inhibited the maturation and antigen-presenting ability of DCs. We next examined a potential involvement of microRNAs (miRNAs). Analyses of avian DCs stimulated with avian IAV identified 9 upregulated and 10 downregulated miRNAs. Curiously, however, NS2-transfection did not alter miRNA expression in DCs, We found that NS2 binds to exportin 5 (Xpo5), which inhibited miRNA biogenesis. Thus, hijacking of the miRNA biogenesis pathway appears to be one mechanism by which NS2 impairs antigen presentation. Furthermore, we found that NS2 directly interacts with interferon regulatory factor 3, which also inhibits the antigen-presenting ability of DCs. These results thus indicate that NS2-mediated impairment of antigen presentation by DCs might be a mechanism that contributes to the prevalence of the influenza virus. Funding Statement: This work was supported by the National Key Research and Development Program of China (2017YFD500706), the Jiangsu Excellent Youth Natural Science Foundation (BK20190077), the National Natural Science Foundation of China (No. 31702197, 31930109, and 31772777), the Fundamental Research Funds for the Central Universities (JCQY201906), the Fundamental Research Funds for the Central Universities (KJQN2018034) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Declaration of Interests: The authors of this editorial have no conflicts of interest to declare. The authors have no other relevant affiliations or financial involvement in any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Ethics Approval Statement: This study was approve by the Ethics Committee of Animal Experiments center of Nanjing Agricultural University. All animal studies were approved by the Institutional Animal Care and Use Committee of Nanjing Agricultural University (SYXK-2017-0007), and followed the National Institutes of Health guidelines for the performance of animal experiments.

A review article on swine flu

Swine flu, also called Hog or Pig Flu, is a contamination because of someone of the several forms of Swine Influenza Virus (SIV). It is common place through pig populace worldwide. Until now only folks were inside the direct contact with pigs were found to get swine flu. But, H1N1 virus is a brand new swine flu virus and it includes the genetic material of swine, hen and human influenza virus. H1N1 influenza or swine flu is a contagious disease this is as a result of the influenza virus. Infection with the H1N1 influenza virus can bring about intense illness and lifestyles threatening complications. Symptoms of H1N1 flu are similar to the ones of the common place flu and scientists are actively reading the scenario to better recognize its variety of signs and how it is spread. The intensity of this disorder may be lowered with the aid of diagnosing and taking proper treatments.

Detection and discrimination of influenza B Victoria lineage deletion variant viruses by real-time RT-PCR.

BackgroundDuring the 2016/17 influenza season, influenza B/VIC lineage variant viruses emerged with two (K162N163) or three (K162N163D164) amino acid (aa) deletions in the haemagglutinin (HA) protein. There are currently five antigenically distinct HA proteins expressed by co-circulating influenza B viruses: B/YAM, B/VIC V1A (no deletion), B/VIC V1A-2DEL (2 aa deletion) and two antigenically distinguishable groups of B/VIC V1A-3DEL (3 aa deletion). The prevalence of these viruses differs across geographical regions, making it critical to have a sensitive, rapid diagnostic assay that detects and distinguishes these influenza B variant viruses during surveillance.AimOur objective was to develop a real-time RT-PCR (rRT-PCR) assay for detection and discrimination of influenza B/VIC lineage variant viruses.MethodsWe designed a diagnostic assay with one pair of conserved primers and three probes specific to each genetic group. We used propagated influenza B/VIC variant viruses and clinical specimens to assess assay performance.ResultsThis rRT-PCR assay detects and distinguishes the influenza B/VIC V1A, B/VIC V1A-2DEL, and B/VIC V1A-3DEL variant viruses, with no cross-reactivity. This assay can be run as a multiplex reaction, allowing for increased testing efficiency and reduced cost.ConclusionCoupling this assay with the Centers for Disease Control and Prevention’s Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Influenza B Lineage Genotyping Kit results in rapid detection and characterisation of circulating influenza B viruses. Detailed surveillance information on these distinct influenza B variant viruses will provide insight into their prevalence and geographical distribution and could aid in vaccine recommendations.

Host Receptors of Influenza Viruses and Coronaviruses-Molecular Mechanisms of Recognition.

Among the four genera of influenza viruses (IVs) and the four genera of coronaviruses (CoVs), zoonotic αIV and βCoV have occasionally caused airborne epidemic outbreaks in humans, who are immunologically naïve, and the outbreaks have resulted in high fatality rates as well as social and economic disruption and losses. The most devasting influenza A virus (IAV) in αIV, pandemic H1N1 in 1918, which caused at least 40 million deaths from about 500 million cases of infection, was the first recorded emergence of IAVs in humans. Usually, a novel human-adapted virus replaces the preexisting human-adapted virus. Interestingly, two IAV subtypes, A/H3N2/1968 and A/H1N1/2009 variants, and two lineages of influenza B viruses (IBV) in βIV, B/Yamagata and B/Victoria lineage-like viruses, remain seasonally detectable in humans. Both influenza C viruses (ICVs) in γIV and four human CoVs, HCoV-229E and HCoV-NL63 in αCoV and HCoV-OC43 and HCoV-HKU1 in βCoV, usually cause mild respiratory infections. Much attention has been given to CoVs since the global epidemic outbreaks of βSARS-CoV in 2002–2004 and βMERS-CoV from 2012 to present. βSARS-CoV-2, which is causing the ongoing COVID-19 pandemic that has resulted in 890,392 deaths from about 27 million cases of infection as of 8 September 2020, has provoked worldwide investigations of CoVs. With the aim of developing efficient strategies for controlling virus outbreaks and recurrences of seasonal virus variants, here we overview the structures, diversities, host ranges and host receptors of all IVs and CoVs and critically review current knowledge of receptor binding specificity of spike glycoproteins, which mediates infection, of IVs and of zoonotic, pandemic and seasonal CoVs.

Ongoing genetic evolution of H9N2 avian influenza viruses in Iranian industrial poultry farms.

Despite the use of wide-scale vaccination programmes against the H9N2 virus, enzootic outbreaks of H9N2 avian influenza (AI) have often occurred and caused serious nationwide economic losses, particularly in broiler chickens. In this study, the haemagglutinin (HA) and neuraminidase (NA) genes of nine recent H9N2s and a common vaccine strain were fully sequenced and compared with other representative Iranian viruses. Phylogenetic analysis revealed that all Iranian viruses were grouped into the G1 sub-lineage with different clusters in which recent isolates (2014-2017) formed a distinct cluster compared to the vaccine group (1998-2004). All Iranian H9N2s exhibited low pathogenicity AI connecting peptide feature with an R/KSSR motif. Amino acid 226, located in the 220 loop of the receptor binding site, was leucine among the recent Iranian viruses, a characteristic of human influenza viruses. With an overall gradual increase in the genetic diversity of H9N2s, Bayesian skyline plots of Iranian HA and NA genes depicted a fluctuation and a relative stable situation, respectively. It is recommended to apply constant surveillance to assess any increase in viral human adaptation and evolutionary changes in circulating field H9N2s. Moreover, antigenic characterisation of the prevailing H9N2 viruses seems to be necessary for evaluating the possible antigenic drift from the vaccine strain.

A chimeric influenza hemagglutinin delivered by parainfluenza virus 5 vector induces broadly protective immunity against genetically divergent influenza a H1 viruses in swine

Pigs are an important reservoir for human influenza viruses, and influenza causes significant economic loss to the swine industry. As demonstrated during the 2009 H1N1 pandemic, control of swine influenza virus infection is a critical step toward blocking emergence of human influenza virus. An effective vaccine that can induce broadly protective immunity against heterologous influenza virus strains is critically needed. In our previous studies [McCormick et al., 2015; PLoS One, 10(6):e0127649], we used molecular breeding (DNA shuffling) strategies to increase the breadth of the variable and conserved epitopes expressed within a single influenza A virus chimeric hemagglutinin (HA) protein. Chimeric HAs were constructed using parental HAs from the 2009 pandemic virus and swine influenza viruses that had a history of zoonotic transmission to humans. In the current study, we used parainfluenza virus 5 (PIV-5) as a vector to express one of these chimeric HA antigens, HA-113. Recombinant PIV-5 expressing HA-113 (PIV5-113) were rescued, and immunogenicity and protective efficacy were tested in both mouse and pig models. The results showed that PIV5-113 can protect mice and pigs against challenge with viruses expressing parental HAs. The protective immunity was extended against other genetically diversified influenza H1-expressing viruses. Our work demonstrates that PIV5-based influenza vaccines are efficacious as vaccines for pigs. The PIV5 vaccine vector and chimeric HA-113 antigen are discussed in the context of the development of universal influenza vaccines and the potential contribution of PIV5-113 as a candidate universal vaccine.

Avian influenza can be brought to Azerbaijan by migratory birds

The danger of spontaneous formation of new highly pathogenic and virulent mutants and serovariants in nature and as a result of constant mutations of the avian, swine and human influenza viruses, clinical signs of influenza, pathogenesis, pathoanatomical changes, ways of prevention and the role of migratory birds in the spread of the disease in Azerbaijan, migrating depending on the season. Migration of migratory birds from north to south and back, depending on the season, with passage through the territory of our republic and sometimes remaining wintering, indicates the danger of introduction of disease to us from those countries at any time.

Application of carbon nanomaterials in human virus detection

Human-pathogenic viruses are still a chief reason for illness and death on the globe, as epitomized by the COVID-19 pandemic instigated by a coronavirus in 2020. Multiple novel sensors have been invented because diseases must be detected and diagnosed as early as possible, and recognition methods have to be carried out with minimal invasivity. Sensors have been particularly developed focusing on miniaturization by the use of nanomaterials for fabricating nanosensors. The nano-sized nature of nanomaterials and their exclusive optical, electronical, magnetical, and mechanical attributes can enhance patient care through the use of sensors with minimal invasivity and extreme sensitivity. Amongst the nanomaterials utilized for fabricating nano-sensors, carbon-based nanomaterials are promising as these sensors respond better to signals in various sensing settings. This review provides an overview of the recent developments in carbon nanomaterial-based biosensors for viral recognition based on the biomarkers that arise from the infection, the nucleic acids from the viruses, and the entire virus. The role of carbon nanomaterials is highlighted by the improvement of sensor and recognition functionality. The Dengue virus, Ebola virus, Hepatits virus, human immunodeficiency virus (HIV), influenza virus, Zika virus and Adenovirus are the virus types reviewed to illustrate the implementation of the techniques. Finally, the drawbacks and advantages of carbon nanomaterial-based biosensors for viral recognition are identified and discussed.

Evaluation of the Effectiveness of Metabolites of Bacterial Strains Bacillus thuringiensis against Human Influenza Virus A/Aichi/2/68 (H3N2) In Vitro and In Vivo.

The morphological and physiological characteristics of Bacillus thuringiensis strains were analyzed and conditions for obtaining culture fluid with maximum yield of secreted RNases were determined. Zymographic analysis showed that culture fluid of B. thuringiensis strains along with low-molecular-weight (15-20 kDa) RNases contained enzymes with a molecular weight ~55 kDa and their content depended on the duration and conditions of culturing. Preparations based on B. thuringiensis culture fluid were effective against human influenza virus A/Aichi/2/68 (H3N2). In experiments on mice infected with 10 LD50 influenza virus strain A/Aichi/2/68 (H3N2), we selected effective variants of preparations based on culture fluid of B. thuringiensi strains for preventive administration that provided reliable protection of infected animals (protection coefficient 50%), close to that of the reference drug Tamiflu.

Detection of H1 Swine Influenza A Virus Antibodies in Human Serum Samples by Age Group1.

Most H1 influenza A viruses (IAVs) of swine are derived from past human viruses. As human population immunity against these IAVs gradually decreases, the risk of reintroduction to humans increases. We examined 549 serum samples from persons 0–97 years of age collected in Belgium during 2017–2018 for hemagglutination inhibiting and virus neutralizing antibodies against 7 major H1 swine IAV (swIAV) clades and 3 human progenitor IAVs. Seroprevalence (titers >40) rates were >50% for classical swine and European human-like swIAVs, >24% for North American human-like δ1a and Asian avian-like swIAVs, and <10% for North American human-like δ1b and European avian-like swIAVs, but rates were age-dependent. Antibody titers against human-like swIAVs and supposed human precursor IAVs correlated with correlation coefficients of 0.30–0.86. Our serologic findings suggest that European avian-like, clade 1C.2.1, and North American human-like δ1b, clade 1B.2.2.2, H1 swIAVs pose the highest pandemic risk.

Mutation of the second sialic acid-binding site of influenza A virus neuraminidase drives compensatory mutations in hemagglutinin.

Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics. Most pandemics occurred upon adaptation of avian IAVs to humans. This adaptation includes a hallmark receptor-binding specificity switch of hemagglutinin (HA) from avian-type α2,3- to human-type α2,6-linked sialic acids. Complementary changes of the receptor-destroying neuraminidase (NA) are considered to restore the precarious, but poorly described, HA-NA-receptor balance required for virus fitness. In comparison to the detailed functional description of adaptive mutations in HA, little is known about the functional consequences of mutations in NA in relation to their effect on the HA-NA balance and host tropism. An understudied feature of NA is the presence of a second sialic acid-binding site (2SBS) in avian IAVs and absence of a 2SBS in human IAVs, which affects NA catalytic activity. Here we demonstrate that mutation of the 2SBS of avian IAV H5N1 disturbs the HA-NA balance. Passaging of a 2SBS-negative H5N1 virus on MDCK cells selected for progeny with a restored HA-NA balance. These viruses obtained mutations in NA that restored a functional 2SBS and/or in HA that reduced binding of avian-type receptors. Importantly, a particular HA mutation also resulted in increased binding of human-type receptors. Phylogenetic analyses of avian IAVs show that also in the field, mutations in the 2SBS precede mutations in HA that reduce binding of avian-type receptors and increase binding of human-type receptors. Thus, 2SBS mutations in NA can drive acquisition of mutations in HA that not only restore the HA-NA balance, but may also confer increased zoonotic potential.

Human influenza viruses in South-East and East Asia: a systematic review of seasonal patterns, viral types/subtypes, and antiviral susceptibility pattern in the past two decades

The study aims to evaluate influenza seasonality pattern and identify influenza viral types/subtype as well as their antiviral susceptibility pattern in South-East (SE) and East Asia (E-Asia) with the view of providing useful information for public health action. The study is a systematic review of existing literature involving the use of search engines such as Google Scholar, PubMed and EBSCOHOST. The search was conducted using a multi-stage approach which yielded 66 articles after screening for relevance to the subject using specific inclusion and exclusion criteria. A total of 60 articles were eventually analyzed and the findings were presented in tables and bar charts. The study showed that the influenza virus was more prevalent in the 6-20 years age group (SE: 53.3% and E-Asia: 44.8%) and also occurred commonly in the age of 61-90 years age group (SE: 15.6% and E-Asia: 24.1%). Seasonal peaks were reported more in the winter period with influenza A (H1N1) pdm09 (22.37%; 24.14%), seasonal influenza A (H1N1) (6.58%; 17.24%), A (H3N2) (11.84%; 17.24%), and influenza B Victoria/Yamagata (5.26%; 20.69%) being the predominant viral type/subtypes. The pathogenic avian influenza strains; AH5N1 (7.89%) and A (H7N9) (6.90%) was also reported in SE and E-Asia respectively. Oseltamivir (37.5%) and peramivir (37.04%) were the most frequently used anti-influenza agents in SE and E-Asia respectively. However, an H55Y+I436N combined mutation 4 (12.5%) and an H274Y amino acid substitution 5 (18.5%) in the neuraminidase gene of influenza A (H1N1) pdm09 was associated with decreased sensitivity to neuraminidase inhibitors. The study has shown that influenza A (H1N1) pandemic and seasonal strain, A (H3N2), and B Victoria/Yamagata remains the predominant circulating virus in SE and E-Asia. However, the dynamic antigenic and genetic evolution of the virus calls for more frequent surveillance in the region.

HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells.

Seasonal influenza virus infections cause 290,000-650,000 deaths annually and severe morbidity in 3-5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαβ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαβ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases.

Antigenicity prediction and vaccine recommendation of human influenza virus A (H3N2) using convolutional neural networks

ABSTRACT The rapid evolution of influenza A viruses poses a great challenge to vaccine development. Analytical and machine learning models have been applied to facilitate the process of antigenicity determination. In this study, we designed deep convolutional neural networks (CNNs) to predict Influenza antigenicity. Our model is the first that systematically analyzed 566 amino acid properties and 141 amino acid substitution matrices for their predictability. We then optimized the structure of the CNNs using particle swarm optimization. The optimal neural networks outperform other predictive models with a blind validation accuracy of 95.8%. Further, we applied our model to vaccine recommendations in the period 1997 to 2011 and contrasted the performance of previous vaccine recommendations using traditional experimental approaches. The results show that our model outperforms the WHO recommendation and other existing models and could potentially improve the vaccine recommendation process. Our results show that WHO often selects virus strains with small variation from year to year and learns slowly and recovers once coverage dips very low. In contrast, the influenza strains selected via our CNN model can differ quite drastically from year to year and exhibit consistently good coverage. In summary, we have designed a comprehensive computational pipeline for optimizing a CNN in the modeling of Influenza A antigenicity and vaccine recommendation. It is more cost and time-effective when compared to traditional hemagglutination inhibition assay analysis. The modeling framework is flexible and can be adopted to study other type of viruses.

Theacrine and strictinin, two major ingredients for the anti-influenza activity of Yunnan Kucha tea

Ethnopharmacological relevanceKucha tea plant (Camellia assamica var. kucha Chang et Wang) is regarded as a mutant variety of wild Pu'er tea plant found in few mountain areas of Yunnan, China. Its fresh young leaves and shoots are picked by the indigenous aborigines in these local areas to prepare an herbal tea for the treatment of common cold empirically. Materials and methodsTwo extra compounds of relative abundance were detected in Kucha tea in comparison with Pu'er tea, and their chemical structures were identified as chlorogenic acid and theacrine. These two compounds as well as two major compounds, strictinin and caffeine, in Kucha tea were evaluated for their cytotoxicity and inhibitory effects on human influenza virus A/Puerto Rico/8/34 by analyzing viral protein expression and progeny production. ResultsNo or low cytotoxicity was detected for the four Kucha compounds when their concentrations were below 100 μM. Expression of viral NS1 protein was significantly inhibited by chlorogenic acid, theacrine or strictinin, but not caffeine at a concentration of 100 μM. The relative inhibitory potency was detected as chlorogenic acid < theacrine < strictinin, and both theacrine and strictinin displayed significant inhibition at a concentration of 50 μM. According to a plaque assay, viral progeny production was significantly reduced by theacrine or strictinin, but not by chlorogenic acid or caffeine under the same concentration of 100 μM. ConclusionIt is suggested that theacrine and strictinin are two major ingredients responsible for the anti-influenza activity of Yunnan Kucha tea traditionally used for the treatment of common cold.

Bayesian inference of reassortment networks reveals fitness benefits of reassortment in human influenza viruses.

Reassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. Here, we introduce a coalescent-based model that allows us to explicitly model the joint coalescent and reassortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. This algorithm provides the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full-genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks showing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.

Guidance for the management of adult patients with coronavirus disease 2019.

In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19). On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.

Genetic Characterization of Influenza A Viruses in Japanese Swine in 2015 to 2019.

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 to 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 21 sampled 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 to 2019, A(H1N1)pdm09 viruses repeatedly became introduced into farms and reassorted with endemic H1N2 and H3N2 IAVs-S. H3N2 IAVs-S isolated during 2015 to 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 hemagglutinin (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 for 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.IMPORTANCE 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 to 2019 yielded H1N1, H1N2, and H3N2 viruses. H1 genes in Japanese swine formed a 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.

Longitudinal sampling is required to maximize detection of intrahost A/H3N2 virus variants.

Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4–7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.

Potential for elimination of SAR-CoV-2 through vaccination as inspired by elimination of multiple influenza viruses through natural pandemics or mass vaccination.

The ongoing pandemic of coronavirus disease 2019 (COVID‐19) caused by the novel virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has claimed many lives worldwide. To combat the pandemic, multiple types of vaccines are under development with unprecedented rapidity. Theoretically, future vaccination against COVID‐19 may fall into long‐term costly guerrilla warfare between SARS‐CoV‐2 and humans. Elimination of SARS‐CoV‐2 through vaccination to avoid the potential long‐term costly guerrilla warfare, if possible, is highly desired and worth intensive consideration. Human influenza pandemics emerging in 1957, 1968, and 2009 established strong global herd immunity and led to the elimination of three human influenza viruses, which circulated worldwide for years before the pandemics. Moreover, both clade 7.2 of subtype H5 highly pathogenic avian influenza virus and subtype H7N9 avian influenza virus circulated in poultry in China for years, and they have been virtually eliminated through mass vaccination in recent years. These facts suggest that the rapid establishment of global herd immunity through mass vaccination using an appropriate vaccine could eliminate SARS‐CoV‐2. The coming 2 years are a golden time for elimination through vaccination, which requires tremendous national and international collaboration. This review also prioritizes the efficacy of vaccines for COVID‐19 and elucidates the importance of the development of more live vaccines for COVID‐19.