Publications by authors named "Yoshihiro Sakoda"

190 Publications

Efficacy of Oral Vaccine against Classical Swine Fever in Wild Boar and Estimation of the Disease Dynamics in the Quantitative Approach.

Viruses 2021 02 20;13(2). Epub 2021 Feb 20.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-Ku, Sapporo 060-0818, Hokkaido, Japan.

Classical swine fever virus (CSFV) in the wild boar population has been spreading in Japan, alongside outbreaks on pigs, since classical swine fever (CSF) reemerged in September 2018. The vaccination using oral bait vaccine was initially implemented in Gifu prefecture in March 2019. In the present study, antibodies against CSFV in wild boar were assessed in 1443 captured and dead wild boars in Gifu prefecture. After the implementation of oral vaccination, the increase of the proportion of seropositive animals and their titer in wild boars were confirmed. Quantitative analysis of antigen and antibodies against CSFV in wild boar implies potential disease diversity in the wild boar population. Animals with status in high virus replication (Ct < 30) and non- or low-immune response were confirmed and were sustained at a certain level after initial oral vaccination. Through continuous vaccination periods, the increase of seroprevalence among wild boar and the decrease of CSFV-positive animals were observed. The epidemiological analysis based on the quantitative virological outcomes could provide more information on the efficacy of oral vaccination and dynamics of CSF in the wild boar population, which will help to improve the implementation of control measures for CSF in countries such as Japan and neighboring countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13020319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924559PMC
February 2021

Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis.

Virology 2021 May 22;557:55-61. Epub 2021 Feb 22.

Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE) Hokkaido University, Sapporo, Japan; Collaborating Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University, Nagasaki, Japan. Electronic address:

Genetic reassortment of influenza A viruses through cross-species transmission contributes to the generation of pandemic influenza viruses. To provide information on the ecology of influenza viruses, we have been conducting a global surveillance of zoonotic influenza and establishing an influenza virus library. Of 4580 influenza virus strains in the library, 3891 have been isolated from over 70 different bird species. The remaining 689 strains were isolated from humans, pigs, horses, seal, whale, and the environment. Phylogenetic analyses of the HA genes of the library isolates demonstrate that the library strains are distributed to all major known clusters of the H1, H2 and H3 subtypes of HA genes that are prevalent in humans. Since past pandemic influenza viruses are most likely genetic reassortants of zoonotic and seasonal influenza viruses, a vast collection of influenza A virus strains from various hosts should be useful for vaccine preparation and diagnosis for future pandemics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2021.02.005DOI Listing
May 2021

A New Variant Among Newcastle Disease Viruses Isolated in the Democratic Republic of the Congo in 2018 and 2019.

Viruses 2021 Jan 20;13(2). Epub 2021 Jan 20.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.

Newcastle disease (ND) is a highly transmissible and devastating disease that affects poultry and wild birds worldwide. Comprehensive knowledge regarding the characteristics and epidemiological factors of the ND virus (NDV) is critical for the control and prevention of ND. Effective vaccinations can prevent and control the spread of the NDV in poultry populations. For decades, the Democratic Republic of the Congo (DRC) has reported the impacts of ND on commercial and traditional poultry farming systems. The reports were preliminary clinical observations, and few cases were confirmed in the laboratory. However, data on the phylogenetic, genetic, and virological characteristics of NDVs circulating in the DRC are not available. In this study, the whole-genome sequences of three NDV isolates obtained using the next-generation sequencing method revealed two isolates that were a new variant of NDV, and one isolate that was clustered in the subgenotype VII.2. All DRC isolates were velogenic and were antigenically closely related to the vaccine strains. Our findings reveal that despite the circulation of the new variant, ND can be controlled in the DRC using the current vaccine. However, epidemiological studies should be conducted to elucidate the endemicity of the disease so that better control strategies can be implemented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13020151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909526PMC
January 2021

Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness.

Vaccines (Basel) 2020 Dec 16;8(4). Epub 2020 Dec 16.

Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-Ku, Sapporo 060-0818, Japan.

H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines8040768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765658PMC
December 2020

Re-Invasion of H5N8 High Pathogenicity Avian Influenza Virus Clade 2.3.4.4b in Hokkaido, Japan, 2020.

Viruses 2020 12 14;12(12). Epub 2020 Dec 14.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Hokkaido, Japan.

Global dispersion of high pathogenicity avian influenza (HPAI), especially that caused by H5 clade 2.3.4.4, has threatened poultry industries and, potentially, human health. An HPAI virus, A/northern pintail/Hokkaido/M13/2020 (H5N8) (NP/Hok/20) belonging to clade 2.3.4.4b, was isolated from a fecal sample collected at a lake in Hokkaido, Japan where migratory birds rested, October 2020. In the phylogenetic trees of all eight gene segments, NP/Hok/20 fell into in the cluster of European isolates in 2020, but was distinct from the isolates in eastern Asia and Europe during the winter season of 2017-2018. The antigenic cartography indicates that the antigenicity of NP/Hok/20 was almost the same as that of previous isolates of H5 clade 2.3.4.4b, whereas the antigenic distances from NP/Hok/20 to the representative strains in clade 2.3.4.4e and to a strain in 2.3.4 were apparently distant. These data imply that HPAI virus clade 2.3.4.4b should have been delivered by bird migration despite the intercontinental distance, although it was not defined whether NP/Hok/20 was transported from Europe via Siberia where migratory birds nest in the summer season. Given the probability of perpetuation of transmission in the northern territory, periodic updates of intensive surveys on avian influenza at the global level are essential to prepare for future outbreaks of the HPAI virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12121439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764937PMC
December 2020

Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens.

Viruses 2020 12 8;12(12). Epub 2020 Dec 8.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.

Control measures in the case of high pathogenicity avian influenza (HPAI) outbreaks in poultry include culling, surveillance, and biosecurity; wild birds in captivity may also be culled, although some rare bird species should be rescued for conservation. In this study, two anti-influenza drugs, baloxavir marboxil (BXM) and peramivir (PR), used in humans, were examined in treating HPAI in birds, using chickens as a model. Chickens were infected with H5N6 HPAI virus and were treated immediately or 24 h from challenge with 20 mg/kg BXM or PR twice a day for five days. As per our findings, BXM significantly reduced virus replication in organs and provided full protection to chickens compared with that induced by PR. In the 24-h-delayed treatment, neither drug completely inhibited virus replication nor ensured the survival of infected chickens. A single administration of 2.5 mg/kg of BXM was determined as the minimum dose required to fully protect chickens from HPAI virus; the concentration of baloxavir acid, the active form of BXM, in chicken blood at this dose was sufficient for a 48 h antiviral effect post-administration. Thus, these data can be a starting point for the use of BXM and PR in treating captive wild birds infected with HPAI virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12121407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762593PMC
December 2020

Efficacy of a Cap-Dependent Endonuclease Inhibitor and Neuraminidase Inhibitors against H7N9 Highly Pathogenic Avian Influenza Virus Causing Severe Viral Pneumonia in Cynomolgus Macaques.

Antimicrob Agents Chemother 2021 02 17;65(3). Epub 2021 Feb 17.

Division of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan

H7N9 highly pathogenic avian influenza virus (HPAIV) infection in a human was first reported in 2017. A/duck/Japan/AQ-HE29-22/2017 (H7N9) (Dk/HE29-22), found in imported duck meat at an airport in Japan, possesses a hemagglutinin with a multibasic cleavage site, indicating high pathogenicity in chickens, as in the case of other H7 HPAIVs. In the present study, we examined the pathogenicity of Dk/HE29-22 and the effectiveness of a cap-dependent endonuclease inhibitor (baloxavir) and neuraminidase inhibitors (oseltamivir and zanamivir) against infection with this strain in a macaque model ( = 3 for each group). All of the macaques infected with Dk/HE29-22 showed severe signs of disease and pneumonia even after the virus had disappeared from lung samples. Virus titers in macaques treated with baloxavir were significantly lower than those in the other treated groups. After infection, levels of interferon alpha and beta (IFN-α and IFN-β) in the blood of macaques in the baloxavir group were the highest among the groups, whereas levels of tumor necrosis factor alpha (TNF-α) and interleukin 13 (IL-13) were slightly increased in the untreated group. In addition, immune checkpoint proteins, including programmed death 1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), were expressed at high levels in the untreated group, especially in one macaque that showed severe signs of disease, indicating that negative feedback responses against vigorous inflammation may contribute to disease progression. In the group treated with baloxavir, the percentages of PD-1-, CTLA-4-, and TIGIT-positive T lymphocytes were lower than those in the untreated group, indicating that reduction in virus titers may prevent expression of immune checkpoint molecules from downregulation of T cell responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01825-20DOI Listing
February 2021

The clinically used serine protease inhibitor nafamostat reduces influenza virus replication and cytokine production in human airway epithelial cells and viral replication in mice.

J Med Virol 2021 Jun 17;93(6):3484-3495. Epub 2020 Dec 17.

Virus Research Center, Clinical Research Division, Sendai Medical Center, Sendai, Japan.

The effects of the clinically used protease inhibitor nafamostat on influenza virus replication have not been well studied. Primary human tracheal (HTE) and nasal (HNE) epithelial cells were pretreated with nafamostat and infected with the 2009 pandemic [A/Sendai-H/108/2009/(H1N1) pdm09] or seasonal [A/New York/55/2004(H3N2)] influenza virus. Pretreatment with nafamostat reduced the titers of the pandemic and seasonal influenza viruses and the secretion of inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, in the supernatants of the cells infected with the pandemic influenza virus. HTE and HNE cells exhibited mRNA and/or protein expression of transmembrane protease serine 2 (TMPRSS2), TMPRSS4, and TMPRSS11D. Pretreatment with nafamostat reduced cleavage of the precursor protein HA0 of the pandemic influenza virus into subunit HA1 in HTE cells and reduced the number of acidic endosomes in HTE and HNE cells where influenza virus RNA enters the cytoplasm. Additionally, nafamostat (30 mg/kg/day, intraperitoneal administration) reduced the levels of the pandemic influenza virus [A/Hyogo/YS/2011 (H1N1) pdm09] in mouse lung washes. These findings suggest that nafamostat may inhibit influenza virus replication in human airway epithelial cells and mouse lungs and reduce infection-induced airway inflammation by modulating cytokine production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753675PMC
June 2021

Cell-penetrating peptide-mediated cell entry of H5N1 highly pathogenic avian influenza virus.

Sci Rep 2020 10 22;10(1):18008. Epub 2020 Oct 22.

Molecular Medical Research Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.

H5N1 highly pathogenic avian influenza virus (HPAIV) poses a huge threat to public health and the global economy. These viruses cause systemic infection in poultry and accidental human infection leads to severe pneumonia, associated with high mortality rates. The hemagglutinin (HA) of H5N1 HPAIV possesses multiple basic amino acids, as in the sequence RERRRKKR at the cleavage site; however, the role of this motif is not fully understood. Here, we showed that a 33-amino acid long peptide derived from HA of H5N1 HPAIV (HA314-46) has the potential to penetrate various cells and lung tissue through a sialic acid-independent endocytotic pathway. Mutant peptide analyses revealed that the cysteine residue at position 318 and multiple basic amino acids were essential for the cell-penetrating activity. Moreover, reassortant viruses possessing H5 HA could enter sialic acid-deficient cells, and virus internalisation was facilitated by cleavage with recombinant furin. Thus, our findings demonstrate that the HA314-46 motif exhibits cell-penetrating activity through a sialic acid-independent cell entry mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74604-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582914PMC
October 2020

Data mining and model-predicting a global disease reservoir for low-pathogenic Avian Influenza (A) in the wider pacific rim using big data sets.

Sci Rep 2020 10 8;10(1):16817. Epub 2020 Oct 8.

University of Alaska Anchorage (UAA), Anchorage, USA.

Avian Influenza (AI) is a complex but still poorly understood disease; specifically when it comes to reservoirs, co-infections, connectedness and wider landscape perspectives. Low pathogenic (Low-path LP) AI in chickens caused by less virulent strains of AI viruses (AIVs)-when compared with highly pathogenic AIVs (HPAIVs)-are not even well-described yet or known how they contribute to wider AI and immune system issues. Co-circulation of LPAIVs with HPAIVs suggests their interactions in their ecological aspects. Here we show for the Pacific Rim an international approach how to data mine and model-predict LP AI and its ecological niche with machine learning and open access data sets and geographic information systems (GIS) on a 5 km pixel size for best-possible inference. This is based on the best-available data on the issue (~ 40,827 records of lab-analyzed field data from Japan, Russia, Vietnam, Mongolia, Alaska and Influenza Research Database (IRD) and U.S. Department of Agriculture (USDA) database sets, as well as 19 GIS data layers). We sampled 157 hosts and 110 low-path AIVs with 32 species as drivers. The prevalence across low-path AIV subtypes is dominated by Muscovy ducks, Mallards, Whistling Swans and gulls also emphasizing industrial impacts for the human-dominated wildlife contact zone. This investigation sets a good precedent for the study of reservoirs, big data mining, predictions and subsequent outbreaks of HPAI and other pandemics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-73664-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545095PMC
October 2020

Classical swine fever virus: the past, present and future.

Virus Res 2020 11 6;289:198151. Epub 2020 Sep 6.

The Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, Bern, Switzerland.

Classical swine fever (CSF) is among the most relevant viral epizootic diseases of swine. Due to its severe economic impact, CSF is notifiable to the world organisation for animal health. Strict control policies, including systematic stamping out of infected herds with and without vaccination, have permitted regional virus eradication. Nevertheless, CSF virus (CSFV) persists in certain areas of the world and has re-emerged regularly. This review summarizes the basic established knowledge in the field and provides a comprehensive and updated overview of the recent advances in fundamental CSFV research, diagnostics and vaccine development. It covers the latest discoveries on the genetic diversity of pestiviruses, with implications for taxonomy, the progress in understanding disease pathogenesis, immunity against acute and persistent infections, and the recent findings in virus-host interactions and virulence determinants. We also review the progress and pitfalls in the improvement of diagnostic tools and the challenges in the development of modern and efficacious marker vaccines compatible with serological tests for disease surveillance. Finally, we highlight the gaps that require research efforts in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2020.198151DOI Listing
November 2020

Oral Supplementation of the Vitamin D Metabolite 25(OH)D Against Influenza Virus Infection in Mice.

Nutrients 2020 Jul 5;12(7). Epub 2020 Jul 5.

Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo 060-0818, Japan.

Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D [25(OH)D], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D and were challenged with the influenza virus. In the lungs of 25(OH)D-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu12072000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400405PMC
July 2020

Detection of avian influenza virus: a comparative study of the in silico and in vitro performances of current RT-qPCR assays.

Sci Rep 2020 05 21;10(1):8441. Epub 2020 May 21.

Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell'Università, 10, Legnaro, Padova, 35020, Italy.

Avian influenza viruses (AIV) are negative sense RNA viruses posing a major threat to the poultry industry worldwide, with the potential to spread to mammals, including humans; hence, an accurate and rapid AIV diagnosis is essential. To date AIV detection relies on molecular methods, mainly RT-qPCR directed against AIV M gene segment. The evolution of AIV represents a relevant issue in diagnostic RT-qPCR due to possible mispriming and/or probe-binding failures resulting in false negative results. Consequently, RT-qPCR for AIV detection should be periodically re-assessed both in silico and in vitro. To this end, a specific workflow was developed to evaluate in silico the complementarity of primers and probes of four published RT-qPCR protocols to their target regions. The four assays and one commercially available kit for AIV detection were evaluated both for their analytical sensitivity using eight different viral dilution panels and for their diagnostic performances against clinical specimens of known infectious status. Differences were observed among the tests under evaluation, both in terms of analytical sensitivity and of diagnostic performances. This finding confirms the importance of continuously monitoring the primers and probes complementarity to their binding regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-64003-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242438PMC
May 2020

Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019.

Virus Genes 2020 Aug 19;56(4):472-479. Epub 2020 May 19.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, 060-0818, Japan.

The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11262-020-01764-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235438PMC
August 2020

Efficacy of Neuraminidase Inhibitors against H5N6 Highly Pathogenic Avian Influenza Virus in a Nonhuman Primate Model.

Antimicrob Agents Chemother 2020 06 23;64(7). Epub 2020 Jun 23.

Division of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Japan.

Attention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used nonhuman primates to elucidate the pathogenesis of H5N6 HPAIV as well as to determine the efficacy of antiviral drugs against the virus. H5N6 HPAIV infection led to high fever in cynomolgus macaques. The lung injury caused by the virus was severe, with diffuse alveolar damage and neutrophil infiltration. In addition, an increase in interferon alpha (IFN-α) showed an inverse correlation with virus titers during the infection process. Oseltamivir was effective for reducing H5N6 HPAIV propagation, and continuous treatment with peramivir reduced virus propagation and the severity of symptoms in the early stage. This study also showed pathologically severe lung injury states in cynomolgus macaques infected with H5N6 HPAIV, even in those that received early antiviral drug treatments, indicating the need for close monitoring and further studies on virus pathogenicity and new antiviral therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02561-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318037PMC
June 2020

Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.

Antiviral Res 2020 06 6;178:104790. Epub 2020 Apr 6.

Division of Pathogenesis and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan; Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.

Human cases of H7N9 influenza A virus infection have been increasing since 2013. The first choice of treatment for influenza is neuraminidase (NA) inhibitors (NAIs), but there is a concern that NAI-resistant viruses are selected in the presence of NAIs. In our previous study, an H7N9 virus carrying AA substitution of threonine (T) for isoleucine (I) at residue 222 in NA (NA222T, N2 numbering) and an H7N9 virus carrying AA substitution of lysine (K) for arginine (R) at residue 292 in NA (NA292K, N2 numbering) were found in different macaques that had been infected with A/Anhui/1/2013 (H7N9) and treated with NAIs. In the present study, the variant with NA292K showed not only resistance to NAIs but also lower replication activity in MDCK cells than did the virus with wild-type NA, whereas the variant with NA222T, which was less resistant to NAIs, showed replication activity similar to that of the wild-type virus. Next, we examined the pathogenicity of these H7N9 NAI-resistant viruses in macaques. The variants caused clinical signs similar to those caused by the wild-type virus with similar replication potency. However, the virus with NA292K was replaced within 7 days by that with NA292R (same as the wild-type) in nasal samples from macaques infected with the virus with NA292K, i.e. the so-called revertant (wild-type virus) became dominant in the population in the absence of an NAI. These results suggest that the clinical signs observed in macaques infected with the NA292K virus are caused by the NA292K virus and the NA292R virus and that the virus with NA292K may not replicate continuously in the upper respiratory tract of patients without treatment as effectively as the wild-type virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2020.104790DOI Listing
June 2020

Development of a High-Throughput Serum Neutralization Test Using Recombinant Pestiviruses Possessing a Small Reporter Tag.

Pathogens 2020 Mar 4;9(3). Epub 2020 Mar 4.

Laboratory of Microbiology, Division of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.

A serum neutralization test (SNT) is an essential method for the serological diagnosis of pestivirus infections, including classical swine fever, because of the cross reactivity of antibodies against pestiviruses and the non-quantitative properties of antibodies in an enzyme-linked immunosorbent assay. In conventional SNTs, an immunoperoxidase assay or observation of cytopathic effect after incubation for 3 to 7 days is needed to determine the SNT titer, which requires labor-intensive or time-consuming procedures. Therefore, a new SNT, based on the luciferase system and using classical swine fever virus, bovine viral diarrhea virus, and border disease virus possessing the 11-amino-acid subunit derived from NanoLuc luciferase was developed and evaluated; this approach enabled the rapid and easy determination of the SNT titer using a luminometer. In the new method, SNT titers can be determined tentatively at 2 days post-infection (dpi) and are comparable to those obtained by conventional SNTs at 3 or 4 dpi. In conclusion, the luciferase-based SNT can replace conventional SNTs as a high-throughput antibody test for pestivirus infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens9030188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157198PMC
March 2020

Dynamics of Classical Swine Fever Spread in Wild Boar in 2018-2019, Japan.

Pathogens 2020 Feb 13;9(2). Epub 2020 Feb 13.

Veterinary Epidemiology Unit, School of Veterinary Medicine, Rakuno Gakuen University, 582, Bunkyodai Midorimachi, Ebetsu 069-8501, Japan.

The prolongation of the classic swine fever (CSF) outbreak in Japan in 2018 was highly associated with the persistence and widespread of the CSF virus (CSFV) in the wild boar population. To investigate the dynamics of the CSF outbreak in wild boar, spatiotemporal analyses were performed. The positive rate of CSFV in wild boar fluctuated dramatically from March to June 2019, but finally stabilized at approximately 10%. The Euclidean distance from the initial CSF notified farm to the farthest infected wild boar of the day constantly increased over time since the initial outbreak except in the cases reported from Gunma and Saitama prefectures. The two-month-period prevalence, estimated using integrated nested Laplace approximation, reached >80% in half of the infected areas in March-April 2019. The area affected continued to expand despite the period prevalence decreasing up to October 2019. A large difference in the shapes of standard deviational ellipses and in the location of their centroids when including or excluding cases in Gunma and Saitama prefectures indicates that infections there were unlikely to have been caused simply by wild boar activities, and anthropogenic factors were likely involved. The emergence of concurrent space-time clusters in these areas after July 2019 indicated that CSF outbreaks were scattered by this point in time. The results of this epidemiological analysis help explain the dynamics of the spread of CSF and will aid in the implementation of control measures, including bait vaccination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens9020119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169391PMC
February 2020

E190V substitution of H6 hemagglutinin is one of key factors for binding to sulfated sialylated glycan receptor and infection to chickens.

Microbiol Immunol 2020 Apr 5;64(4):304-312. Epub 2020 Feb 5.

Department of Disease Control, Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Avian influenza viruses (AIVs) recognize sialic acid linked α2,3 to galactose (SAα2,3Gal) glycans as receptors. In this study, the interactions between hemagglutinins (HAs) of AIVs and sulfated SAα2,3Gal glycans were analyzed to clarify the molecular basis of interspecies transmission of AIVs from ducks to chickens. It was revealed that E190V and N192D substitutions of the HA increased the recovery of viruses derived from an H6 duck virus isolate, A/duck/Hong Kong/960/1980 (H6N2), in chickens. Recombinant HAs from an H6 chicken virus, A/chicken/Tainan/V156/1999 (H6N1), bound to sulfated SAα2,3Gal glycans, whereas the HAs from an H6 duck virus did not. Binding preference of mutant HAs revealed that an E190V substitution is critical for the recognition of sulfated SAα2,3Gal glycans. These results suggest that the binding of the HA from H6 AIVs to sulfated SAα2,3Gal glycans explains a part of mechanisms of interspecies transmission of AIVs from ducks to chickens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1348-0421.12773DOI Listing
April 2020

Genetic and antigenic characterization of the first H7N7 low pathogenic avian influenza viruses isolated in Vietnam.

Infect Genet Evol 2020 03 21;78:104117. Epub 2019 Nov 21.

Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kitaku, Sapporo, Hokkaido 060-0818, Japan; Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido 001-0020, Japan. Electronic address:

During the annual surveillance of avian influenza viruses (AIVs) in Vietnam in 2018, three H7N7 AIV isolates were identified in domestic ducks in a single flock in Vinh Long province. The present study is the first documented report of H7N7 virus isolates in Vietnam and aimed to characterize these viruses, both genetically and antigenically. Deduced amino acid sequences for the hemagglutinins (HAs) indicated a low pathogenicity of these viruses in chickens. Phylogenetic analysis revealed that the H7 HA genes of these isolates were closely related to each other and belonged to the European-Asian sublineage, together with those of H7N3 viruses isolated from ducks in Cambodia during 2017. They were not genetically related to those of Chinese H7N9 or H7N1 viruses that were previously detected in Vietnam during 2012. Interestingly, the M genes of the two H7N7 virus isolates were phylogenetically classified into distinct groups, suggesting an ongoing reassortment event in domestic ducks because they were isolated from the same flock. These H7N7 viruses exhibited somewhat different antigenic characteristics compared with other representative H7 low pathogenic AIVs. Surprisingly, the antigenicity of Vietnamese H7N7 viruses is similar to Chinese H7N9 highly pathogenic AIV. The findings of this study suggest that H7N7 viruses may be undergoing reassortment and antigenic diversification in poultry flocks in Vietnam. The silent spread of Vietnamese H7N7 viruses in chickens may lead to acquire high pathogenicity in chickens although the zoonotic potential of the viruses seems to be low since these viruses retain typical avian-specific motifs in the receptor-binding site in the HA and there is no mutation related to mammalian adaptation in PB2 gene. Thus, these results highlight the need for continuous and intensive surveillance of avian influenza in Vietnam, targeting not only highly pathogenic AIVs but also low pathogenic viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.meegid.2019.104117DOI Listing
March 2020

A cloned classical swine fever virus derived from the vaccine strain GPE causes cytopathic effect in CPK-NS cells via type-I interferon-dependent necroptosis.

Virus Res 2020 01 9;276:197809. Epub 2019 Nov 9.

Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan; Global Station for Zoonotic Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, Japan. Electronic address:

Classical swine fever viruses (CSFVs) do typically not show cytopathic effect (CPE) in cell culture, while some strains such as vaccine strain the GPE induce CPE in the swine kidney-derived CPK-NS cell line cultured in serum-free medium. These latter strains commonly lack N-mediated inhibition of type-I interferon (IFN) induction. In order to explore the molecular mechanisms of GPE-induced CPE, we analyzed the cellular pathways involved. In CPK-NS cells infected with the attenuated-vaccine-derived vGPE strain, both, apoptosis and necroptosis were induced. Necroptosis was type-I IFN-dependent and critical for visible CPE. In contrast, the parental virulent vALD-A76 strain did not induce any of these pathways nor CPE. We used reverse genetics to investigate which viral factors regulate these cell-death pathways. Interestingly, a mutant vGPE in which the N function was restored to inhibit type-I IFN induction did not induce necroptosis nor CPE but still induced apoptosis, while an N-mutant vALD-A76 incapable of inhibiting type-I IFN production induced necroptosis and CPE. Although E of CSFV is reportedly involved in controlling apoptosis, apoptosis induction by vGPE or apoptosis inhibition by vALD-A76 were independent of the unique amino acid difference found in E of these two strains. Altogether, these results demonstrate that type-I IFN-dependent necroptosis related to non-functional N is the main mechanism for CPE induction by vGPE, and that viral factor(s) other than E may induce or inhibit apoptosis in vGPE or vALD-A76 infected CPK-NS cells, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2019.197809DOI Listing
January 2020

Molecular, antigenic, and pathogenic characterization of H5N8 highly pathogenic avian influenza viruses isolated in the Democratic Republic of Congo in 2017.

Arch Virol 2020 Jan 9;165(1):87-96. Epub 2019 Nov 9.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.

In May 2017, high mortality of chickens and Muscovy ducks due to the H5N8 highly pathogenic avian influenza virus (HPAIV) was reported in the Democratic Republic of Congo (DR Congo). In this study, we assessed the molecular, antigenic, and pathogenic features in poultry of the H5N8 HPAIV from the 2017 Congolese outbreaks. Phylogenetic analysis of the eight viral gene segments revealed that all 12 DR Congo isolates clustered in clade 2.3.4.4B together with other H5N8 HPAIVs isolated in Africa and Eurasia, suggesting a possible common origin of these viruses. Antigenically, a slight difference was observed between the Congolese isolates and a representative virus from group C in the same clade. After intranasal inoculation with a representative DR Congo virus, high pathogenicity was observed in chickens and Muscovy ducks but not in Pekin ducks. Viral replication was higher in chickens than in Muscovy duck and Pekin duck organs; however, neurotropism was pronounced in Muscovy ducks. Our data confirmed the high pathogenicity of the DR Congo virus in chickens and Muscovy ducks, as observed in the field. National awareness and strengthening surveillance in the region are needed to better control HPAIVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-019-04456-xDOI Listing
January 2020

Role of Wild Boar in the Spread of Classical Swine Fever in Japan.

Pathogens 2019 10 24;8(4). Epub 2019 Oct 24.

Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0018, Japan.

Since September 2018, nearly 900 notifications of classical swine fever (CSF) have been reported in Gifu Prefecture (Japan) affecting domestic pig and wild boar by the end of August 2019. To determine the epidemiological characteristics of its spread, a spatio-temporal analysis was performed using actual field data on the current epidemic. The spatial study, based on standard deviational ellipses of official CSF notifications, showed that the disease likely spread to the northeast part of the prefecture. A maximum significant spatial association estimated between CSF notifications was 23 km by the multi-distance spatial cluster analysis. A space-time permutation analysis identified two significant clusters with an approximate radius of 12 and 20 km and 124 and 98 days of duration, respectively. When the area of the identified clusters was overlaid on a map of habitat quality, approximately 82% and 75% of CSF notifications, respectively, were found in areas with potential contact between pigs and wild boar. The obtained results provide information on the current CSF epidemic, which is mainly driven by wild boar cases with sporadic outbreaks on domestic pig farms. These findings will help implement control measures in Gifu Prefecture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens8040206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963481PMC
October 2019

END-phenomenon negative bovine viral diarrhea virus that induces the host's innate immune response supports propagation of BVDVs with different immunological properties.

Virology 2019 12 2;538:97-110. Epub 2019 Oct 2.

School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo, Japan. Electronic address:

Our previous study reported that persistently infected (PI) cattle of bovine viral diarrhea virus (BVDV) have co-infected with BVDV/END and /END that promote and inhibit host's type-I interferon (IFN) production, respectively. However, the relationship between co-infection of immunologically distinct BVDVs and persistent infection as well as the biological significance of END viruses remains unknown. Experiments using cultured cells revealed that END virus, which is unable to propagate in situations where the host's immune response is induced by IFN-α addition, is able to propagate under those conditions when co-infecting with END virus. These results indicate that BVDV/END can coexist with BVDV/END and that co-infection with END viruses supports the propagation of END viruses. Our in vitro experiments strongly suggest that co-infection with END virus is involved in the maintenance of persistent infection of BVDV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2019.09.016DOI Listing
December 2019

Dynamics of Reporter Viruses.

J Virol 2019 11 29;93(22). Epub 2019 Oct 29.

Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

Recombinant viruses possessing reporter proteins have been generated for virus research. In the case of the family , we recently generated recombinant viruses, including the hepatitis C virus of the genus , Japanese encephalitis virus (JEV) of the genus , and bovine viral diarrhea virus of the genus ; all three viruses possess an 11-amino-acid subunit derived from NanoLuc luciferase (HiBiT). Here, we further developed the recombinant viruses and investigated their utility Recombinant viruses harboring HiBiT in the E, NS1, or NS3 protein constructed based on the predicted secondary structure, solvent-accessible surface area, and root mean square fluctuation of the proteins exhibited comparable replication to that of the wild-type virus The recombinant JEV carrying HiBiT in the NS1 protein exhibited propagation in mice comparable to that of the parental virus, and propagation of the recombinant was monitored by the luciferase activity. In addition, the recombinants of classical swine fever virus (CSFV) possessing HiBiT in the E or E2 protein also showed propagation comparable to that of the wild-type virus. The recombinant CSFV carrying HiBiT in E exhibited similar replication to the parental CSFV in pigs, and detection of viral propagation of this recombinant by luciferase activity was higher than that by quantitative PCR (qPCR). Taken together, these results demonstrated that the reporter viruses generated herein are powerful tools for elucidating the viral life cycle and pathogeneses and provide a robust platform for the development of novel antivirals. applications of reporter viruses are necessary to understand viral pathogenesis and provide a robust platform for antiviral development. In developing such applications, determination of an ideal locus to accommodate foreign genes is important, because insertion of foreign genes into irrelevant loci can disrupt the protein functions required for viral replication. Here, we investigated the criteria to determine ideal insertion sites of foreign genes from the protein structure of viral proteins. The recombinant viruses generated by our criteria exhibited propagation comparable to that of parental viruses Our proteomic approach based on the flexibility profile of viral proteins may provide a useful tool for constructing reporter viruses, including viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.01191-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819943PMC
November 2019

Glycan-immobilized dual-channel field effect transistor biosensor for the rapid identification of pandemic influenza viral particles.

Sci Rep 2019 08 12;9(1):11616. Epub 2019 Aug 12.

Research Organization for Nano & Life Innovation, Waseda University, 513 Waseda-tsurumaki-cho, Shinjuku-ku, Tokyo, 162-0041, Japan.

Pandemic influenza, triggered by the mutation of a highly pathogenic avian influenza virus (IFV), has caused considerable damage to public health. In order to identify such pandemic IFVs, antibodies that specifically recognize viral surface proteins have been widely used. However, since the analysis of a newly discovered virus is time consuming, this delays the availability of suitable detection antibodies, making this approach unsuitable for the early identification of pandemic IFVs. Here we propose a label-free semiconductor-based biosensor functionalized with sialic-acid-containing glycans for the rapid identification of the pandemic IFVs present in biological fluids. Specific glycans are able to recognize wild-type human and avian IFVs, suggesting that they are useful in discovering pandemic IFVs at the early stages of an outbreak. We successfully demonstrated that a dual-channel integrated FET biosensing system, which were modified with 6'-sialyllactose and 3'-sialyllactose for each gate area, can directly and specifically detect human H1N1 and avian H5N1 IFV particles, respectively, present in nasal mucus. Furthermore, to examine the possibility of identifying pandemic IFVs, the signal attributed to the detection of Newcastle disease virus (NDV) particles, which was selected as a prime model of a pandemic IFV, was clearly observed from both sensing gates. Our findings suggest that the proposed glycan-immobilized sensing system could be useful in identifying new pandemic IFVs at the source of an outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-48076-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691001PMC
August 2019

Slaughterhouse survey for detection of bovine viral diarrhea infection among beef cattle in Kyushu, Japan.

J Vet Med Sci 2019 Oct 5;81(10):1450-1454. Epub 2019 Aug 5.

Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan.

Bovine viral diarrhea virus (BVDV) footprint has spread across the globe and is responsible for one of the most economically important diseases in cattle. In Japan, some regional surveillance and preventive measures to control bovine viral diarrhea (BVD) have been implemented. However, BVDV infection is poorly understood in cattle industries, and there is no systematic BVD surveillance system and control program. Kyushu is the center for raising beef cattle in Japan. Therefore, this study aimed to determine the BVDV infection using a slaughterhouse survey among beef cattle in Kyushu, Japan. A total of 1,075 blood samples were collected at two regional slaughterhouses in Miyazaki prefecture from December 2015 to June 2016. Antigen ELISA was used for detection of BVDV antigen in blood samples. Two samples showed positive results (2/1,075; 0.18%). BVDV RNA was extracted from positive blood samples; the sequence was determined and analyzed by the neighbor-joining method for construction of the phylogenetic tree. Phylogenetic analysis based on the 5'-UTR revealed that the two positive samples were grouped into the same subtype BVDV-1b in the BVDV-1 genotype, but the infected cattle belonged to two different farms. In conclusion, this is the first study to identify the presence of BVDV in a slaughterhouse survey in Kyushu. These findings suggest that a slaughterhouse survey is a useful tool for developing a surveillance system for monitoring infectious diseases in cattle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.19-0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863731PMC
October 2019

Broad and systemic immune-modulating capacity of plant-derived dsRNA.

Int Immunol 2019 11;31(12):811-821

Laboratory of Molecular Genetics, Institute for Frontier Life and Medical Sciences, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.

Double-stranded RNA (dsRNA) is well characterized as an inducer of anti-viral interferon responses. We previously reported that dsRNA extracted from a specific edible plant possesses an immune-modulating capacity to confer, in mice, resistance against respiratory viruses, including the H1N1 strain of the influenza A virus (IAV). We report here that the systemic immune-activating capacity of the plant-derived dsRNA protected mice from infection by a highly virulent H5N1 strain of the IAV. In addition, subcutaneous inoculation of the dsRNA together with the inactivated virion of the H5N1 strain of the IAV suppressed the lethality of the viral infection as compared with individual inoculation of either dsRNA or HA protein, suggesting its potential usage as a vaccination adjuvant. Moreover, intra-peritoneal inoculation of the dsRNA limited the growth of B16-F10 melanoma cells through the activation of NK cells in murine models. Taken together, this study demonstrated the systemic immune-modulating capacity of a plant-derived dsRNA and its potential for nucleic acid-based clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/intimm/dxz054DOI Listing
November 2019

A systematic study towards evolutionary and epidemiological dynamics of currently predominant H5 highly pathogenic avian influenza viruses in Vietnam.

Sci Rep 2019 05 22;9(1):7723. Epub 2019 May 22.

Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, 060-0818, Japan.

This study aimed to elucidate virus, host and environmental dynamics of Vietnamese H5 highly pathogenic avian influenza viruses (HPAIVs) during 2014-2017. Epidemiologically, H5 HPAIVs were frequently detected in apparently healthy domestic and Muscovy ducks and therefore these are preferred species for H5 HPAIV detection in active surveillance. Virologically, clade 2.3.2.1c and 2.3.4.4 H5 HPAIVs were predominant and exhibited distinct phylogeographic evolution. Clade 2.3.2.1c viruses clustered phylogenetically in North, Central and South regions, whilst clade 2.3.4.4 viruses only detected in North and Central regions formed small groups. These viruses underwent diverse reassortment with existence of at least 12 genotypes and retained typical avian-specific motifs. These H5 HPAIVs exhibited large antigenic distance from progenitor viruses and commercial vaccines currently used in poultry. Bayesian phylodynamic analysis inferred that clade 2.3.2.1c viruses detected during 2014-2017 were likely descended from homologous clade viruses imported to Vietnam previously and/or preexisting Chinese viruses during 2012-2013. Vietnamese clade 2.3.4.4 viruses closely shared genetic traits with contemporary foreign spillovers, suggesting that there existed multiple transboundary virus dispersals to Vietnam. This study provides insights into the evolution of Vietnamese H5 HPAIVs and highlights the necessity of strengthening control measures such as, preventive surveillance and poultry vaccination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-42638-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531488PMC
May 2019