scholarly journals Loss of Fitness of Mexican H7N3 Highly Pathogenic Avian Influenza Virus in Mallards after Circulating in Chickens

2019 ◽  
Vol 93 (14) ◽  
Author(s):  
Sung-Su Youk ◽  
Dong-Hun Lee ◽  
Christina M. Leyson ◽  
Diane Smith ◽  
Miria Ferreira Criado ◽  
...  

ABSTRACTOutbreaks of highly pathogenic avian influenza (HPAI) virus subtype H7N3 have been occurring in commercial chickens in Mexico since its first introduction in 2012. In order to determine changes in virus pathogenicity and adaptation in avian species, three H7N3 HPAI viruses from 2012, 2015, and 2016 were evaluated in chickens and mallards. All three viruses caused high mortality in chickens when given at medium to high doses and replicated similarly. No mortality or clinical signs and similar infectivity were observed in mallards inoculated with the 2012 and 2016 viruses. However, the 2012 H7N3 HPAI virus replicated well in mallards and transmitted to contacts, whereas the 2016 virus replicated poorly and did not transmit to contacts, which indicates that the 2016 virus is less adapted to mallards.In vitro, the 2016 virus grew slower and to lower titers than did the 2012 virus in duck fibroblast cells. Full-genome sequencing showed 115 amino acid differences between the 2012 and the 2016 viruses, with some of these changes previously associated with changes in replication in avian species, including hemagglutinin (HA) A125T, nucleoprotein (NP) M105V, and NP S377N. In conclusion, as the Mexican H7N3 HPAI virus has passaged through large populations of chickens in a span of several years and has retained its high pathogenicity for chickens, it has decreased in fitness in mallards, which could limit the potential spread of this HPAI virus by waterfowl.IMPORTANCENot much is known about changes in host adaptation of avian influenza (AI) viruses in birds after long-term circulation in chickens or other terrestrial poultry. Although the origin of AI viruses affecting poultry is wild aquatic birds, the role of these birds in further dispersal of poultry-adapted AI viruses is not clear. Previously, we showed that HPAI viruses isolated early from poultry outbreaks could still infect and transmit well in mallards. In this study, we demonstrate that the Mexican H7N3 HPAI virus after four years of circulation in chickens replicates poorly and does not transmit in mallards but remains highly pathogenic in chickens. This information on changes in host adaptation is important for understanding the epidemiology of AI viruses and the role that wild waterfowl may play in disseminating viruses adapted to terrestrial poultry.

Author(s):  
Keiichi Taniguchi ◽  
Yoshinori Ando ◽  
Masanori Kobayashi ◽  
Shinsuke Toba ◽  
Haruaki Nobori ◽  
...  

Human infections with the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threatens public health. The susceptibility of HPAIVs to baloxavir acid (BXA), which is a new class of inhibitor for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but has not yet been characterized fully. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants in vitro was assessed. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested to those of seasonal and other zoonotic strains. BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate; A/Hong Kong/483/1997 (H5N1) strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, followed by prevention of acute lung inflammation and improvement of mortality compared with oseltamivir phosphate (OSP). Furthermore, combination treatments with BXM and OSP, using a 48-hour delayed treatment model showed a more potent effect on viral replication in organs, accompanied by improved survival compared to BXM or OSP monotherapy. From each test, no resistant virus (e.g., I38T in the PA) emerged in any BXM-treated mouse. These results therefore support the conclusion that BXM has potent antiviral efficacy against H5 HPAIV infections.


2020 ◽  
Vol 33 (1) ◽  
pp. 124-128
Author(s):  
Tanjin T. Mumu ◽  
Mohammed Nooruzzaman ◽  
Azmary Hasnat ◽  
Rokshana Parvin ◽  
Emdadul H. Chowdhury ◽  
...  

A mixed-aged flock of 130 turkeys in Bangladesh reported the sudden death of 1 bird in September 2017. Highly pathogenic avian influenza A(H5N1) virus was detected in 3 turkeys, and phylogenetic analysis placed the viruses in the reassortant clade 2.3.2.1a. The birds had clinical signs of depression, diarrhea, weakness, closed eyes, and finally death. The mortality rate of the flock was 13% over the 6 d prior to the flock being euthanized. At autopsy, we observed congestion in lungs and brain, hemorrhages in the trachea, pancreas, breast muscle, coronary fat, intestine, bursa of Fabricius, and kidneys. Histopathology revealed hemorrhagic pneumonia, hemorrhages in the liver and kidneys, and hemorrhages and necrosis in the spleen and pancreas. Significant changes in the brain included gliosis, focal encephalomalacia and encephalitis, and neuronophagia.


2009 ◽  
Vol 84 (4) ◽  
pp. 2122-2133 ◽  
Author(s):  
Wenjun Ma ◽  
Dominique Brenner ◽  
Zhongfang Wang ◽  
Bianca Dauber ◽  
Christina Ehrhardt ◽  
...  

ABSTRACT A reassortant avian influenza virus (designated FPV NS GD), carrying the NS-segment of the highly pathogenic avian influenza virus (HPAIV) strain A/Goose/Guangdong/1/96 (GD; H5N1) in the genetic background of the HPAIV strain A/FPV/Rostock/34 (FPV; H7N1), was rescued by reverse genetics. Remarkably, in contrast to the recombinant wild-type FPV (rFPV), the reassortant virus was able to replicate more efficiently in different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, FPV NS GD caused disease and death in experimentally infected mice and was detected in mouse lungs; in contrast, rFPV was not able to replicate in mice effectively. These results indicated an altered host range and increased virulence. Furthermore FPV NS GD showed pronounced pathogenicity in chicken embryos. In an attempt to define the molecular basis for the apparent differences, we determined that NS1 proteins of the H5N1 and H7N1 strains bound the antiviral kinase PKR and the F2F3 domain of cleavage and polyadenylation specificity factor 30 (CPSF30) with comparable efficiencies in vitro. However, FPV NS GD infection resulted in (i) increased expression of NS1, (ii) faster and stronger PKR inhibition, and (iii) stronger beta interferon promoter inhibition than rFPV. Taken together, the results shed further light on the importance of the NS segment of an H5N1 strain for viral replication, molecular pathogenicity, and host range of HPAIVs and the possible consequences of a reassortment between naturally occurring H7 and H5 type HPAIVs.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jin-Yong Noh ◽  
Kyu-Jik Kim ◽  
Sun-Hak Lee ◽  
Jun-Beom Kim ◽  
Deok-Hwan Kim ◽  
...  

Highly pathogenic avian influenza (HPAI) is considered as one of the most devastating poultry diseases. It is imperative to immediately report any known outbreaks to the World Organization for Animal Health. Early detection of infected birds is of paramount importance to control virus spread, thus minimizing the associated economic loss. In this study, thermal imaging camera devices were used to detect change in the maximum surface temperature (MST) of chickens (n = 5) and ducks (n = 2) as an early indicator of experimental HPAI infection. The MST of both chickens and ducks increased at least 24 h before the manifestation of clinical signs of HPAI infection, depending on the severity of the infection. The basal MST was recorded for broiler chickens housed under small pen and normal farm conditions without intentional infection. A threshold cutoff of MST was established based on the circadian rhythm of normal MST. This study suggests that thermal imaging of chickens and ducks is a promising tool to screen any potential HPAI-infected flock in order to expedite HPAI diagnosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Albert Perlas ◽  
Jordi Argilaguet ◽  
Kateri Bertran ◽  
Raúl Sánchez-González ◽  
Miquel Nofrarías ◽  
...  

Highly pathogenic avian influenza viruses (HPAIVs) cause severe systemic disease and high mortality rates in chickens, leading to a huge economic impact in the poultry sector. However, some chickens are resistant to the disease. This study aimed at evaluating the mechanisms behind HPAIV disease resistance. Chickens of different breeds were challenged with H7N1 HPAIV or clade 2.3.4.4b H5N8 HPAIV, euthanized at 3 days post-inoculation (dpi), and classified as resistant or susceptible depending on the following criteria: chickens that presented i) clinical signs, ii) histopathological lesions, and iii) presence of HPAIV antigen in tissues were classified as susceptible, while chickens lacking all these criteria were classified as resistant. Once classified, we performed RNA-Seq from lung and spleen samples in order to compare the transcriptomic signatures between resistant and susceptible chickens. We identified minor transcriptomic changes in resistant chickens in contrast with huge alterations observed in susceptible chickens. Interestingly, six differentially expressed genes were downregulated in resistant birds and upregulated in susceptible birds. Some of these genes belong to the NF-kappa B and/or mitogen-activated protein kinase signaling pathways. Among these six genes, the serine protease-encoding gene PLAU was of particular interest, being the most significantly downregulated gene in resistant chickens. Expression levels of this protease were further validated by RT-qPCR in a larger number of experimentally infected chickens. Furthermore, HPAIV quasi-species populations were constructed using 3 dpi oral swabs. No substantial changes were found in the viral segments that interact with the innate immune response and with the host cell receptors, reinforcing the role of the immune system of the host in the clinical outcome. Altogether, our results suggest that an early inactivation of important host genes could prevent an exaggerated immune response and/or viral replication, conferring resistance to HPAIV in chickens.


Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 111
Author(s):  
Keiichi Taniguchi ◽  
Yoshinori Ando ◽  
Masanori Kobayashi ◽  
Shinsuke Toba ◽  
Haruaki Nobori ◽  
...  

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-h delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.


2016 ◽  
Vol 90 (21) ◽  
pp. 9967-9982 ◽  
Author(s):  
Mary J. Pantin-Jackwood ◽  
Mar Costa-Hurtado ◽  
Eric Shepherd ◽  
Eric DeJesus ◽  
Diane Smith ◽  
...  

ABSTRACTWild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses.IMPORTANCEThe spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the Gs/GD lineage by migratory waterfowl is a serious concern for animal and public health. H5 and H7 HPAI viruses are considered to be adapted to gallinaceous species (chickens, turkeys, quail, etc.) and less likely to infect and transmit in wild ducks. In order to understand why this is different with certain Gs/GD lineage H5 HPAI viruses, we compared the pathogenicity and transmission of several H5 and H7 HPAI viruses from previous poultry outbreaks to Gs/GD lineage H5 viruses, including H5N1 (clade 2.2), H5N8 and H5N2 (clade 2.3.4.4) viruses, in mallards as a representative wild duck species. Surprisingly, most HPAI viruses examined in this study replicated well and transmitted among mallards; however, the three Gs/GD lineage H5 HPAI viruses replicated to higher titers, which could explain the transmission of these viruses in susceptible wild duck populations.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1069
Author(s):  
Sol Jeong ◽  
Jung-Hoon Kwon ◽  
Sun-Hak Lee ◽  
Yu-Jin Kim ◽  
Jei-Hyun Jeong ◽  
...  

Since 2014, H5Nx clade 2.3.4.4 highly pathogenic avian influenza viruses (HPAIV) have caused outbreaks in wild birds and poultry in multiple continents, including Asia, Europe, Africa, and North America. Wild birds were suspected to be the sources of the local and global spreads of HPAIV. This study evaluated the infectivity, pathogenicity, and transmissibility of clade 2.3.4.4 H5N6 HPAIV in mandarin ducks (Aixgalericulata) and domestic pigeons (Columbia livia domestica). None of the birds used in this study, 20 mandarin ducks or 8 pigeons, showed clinical signs or mortality due to H5N6 HPAI infection. Two genotypes of H5N6 HPAIV showed replication and transmission by direct and indirect contact between mandarin ducks. H5N6 HPAIV replicated and transmitted by direct contact between pigeons, although the viral shedding titer and duration were relatively lower and shorter than those in mandarin ducks. Influenza virus antigen was detected in various internal organs of infected mandarin ducks and pigeons, indicating systemic infection. Therefore, our results indicate mandarin ducks and pigeons can be subclinically infected with clade 2.3.4.4 H5N6 HPAIV and transfer the virus to adjacent birds. The role of mandarin ducks and pigeons in the spread and prevalence of clade 2.3.4.4 H5N6 viruses should be carefully monitored.


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