scholarly journals Association of Increased Pathogenicity of Asian H5N1 Highly Pathogenic Avian Influenza Viruses in Chickens with Highly Efficient Viral Replication Accompanied by Early Destruction of Innate Immune Responses

2009 ◽  
Vol 83 (15) ◽  
pp. 7475-7486 ◽  
Author(s):  
Koutaro Suzuki ◽  
Hironao Okada ◽  
Toshihiro Itoh ◽  
Tatsuya Tada ◽  
Masaji Mase ◽  
...  
Keyword(s):  
Immune Responses ◽  
Highly Pathogenic Avian Influenza ◽  
Vascular Endothelial Cells ◽  
Innate Immune ◽  
Vascular Endothelial ◽  
Innate Immune Responses ◽  
Cytokine Mrna ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n1 Hpai

ABSTRACT The Asian H5N1 highly pathogenic avian influenza (HPAI) viruses have been increasing in pathogenicity in diverse avian species since 1996 and are now widespread in Asian, European, and African countries. To better understand the basis of the increased pathogenicity of recent Asian H5N1 HPAI viruses in chickens, we compared the fevers and mean death times (MDTs) of chickens infected with the Asian H5N1 A/chicken/Yamaguchi/7/04 (CkYM7) strain with those infected with the H5N1 Duck/Yokohama/aq10/03 (DkYK10) strain, using a wireless thermosensor. Asian H5N1 CkYM7 caused peracute death in chickens before fever could be induced, whereas DkYK10 virus induced high fevers and had a long MDT. Real-time PCR analyses of cytokine mRNA expressions showed that CkYM7 quickly induced antiviral and proinflammatory cytokine mRNA expressions at 24 h postinfection (hpi) that suddenly decreased at 32 hpi. In contrast, these cytokine mRNA expressions increased at 24 hpi in the DkYK10 group, but decreased from 48 hpi onward to levels similar to those resulting from infection with the low-pathogenicity H5N2 A/chicken/Ibaraki/1/2004 strain. Sequential titrations of viruses in lungs, spleens, and kidneys demonstrated that CkYM7 replicated rapidly and efficiently in infected chickens and that the viral titers were more than twofold higher than those of DkYK10. CkYM7 preferentially and efficiently replicated in macrophages and vascular endothelial cells, while DkYK10 grew moderately in macrophages. These results indicate that the increased pathogenicity in chickens of the recent Asian H5N1 HPAI viruses may be associated with extremely rapid and high replication of the virus in macrophages and vascular endothelial cells, which resulted in disruption of the thermoregulation system and innate immune responses.

scholarly journals Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections

2020 ◽  
Vol 11 ◽  
Author(s):  
Hanaa Ahmed-Hassan ◽  
Brianna Sisson ◽  
Rajni Kant Shukla ◽  
Yasasvi Wijewantha ◽  
Nicholas T. Funderburg ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Highly Pathogenic ◽  
Respiratory Viral Infections

scholarly journals Lassa Virus, but Not Highly Pathogenic New World Arenaviruses, Restricts Immunostimulatory Double-Stranded RNA Accumulation during Infection

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Elizabeth J. Mateer ◽  
Junki Maruyama ◽  
Galen E. Card ◽  
Slobodan Paessler ◽  
Cheng Huang
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Lassa Virus ◽  
Innate Immune Responses ◽  
Highly Pathogenic ◽  
Double Stranded Rna ◽  
L Protein ◽  
Biochemical Assays ◽  
Infected Cells ◽  
First Time

ABSTRACT The arenaviruses Lassa virus (LASV), Junín virus (JUNV), and Machupo virus (MACV) can cause severe and fatal diseases in humans. Although these pathogens are closely related, the host immune responses to these virus infections differ remarkably, with direct implications for viral pathogenesis. LASV infection is immunosuppressive, with a very low-level interferon response. In contrast, JUNV and MACV infections stimulate a robust interferon (IFN) response in a retinoic acid-inducible gene I (RIG-I)-dependent manner and readily activate protein kinase R (PKR), a known host double-stranded RNA (dsRNA) sensor. In response to infection with RNA viruses, host nonself RNA sensors recognize virus-derived dsRNA as danger signals and initiate innate immune responses. Arenavirus nucleoproteins (NPs) contain a highly conserved exoribonuclease (ExoN) motif, through which LASV NP has been shown to degrade virus-derived immunostimulatory dsRNA in biochemical assays. In this study, we for the first time present evidence that LASV restricts dsRNA accumulation during infection. Although JUNV and MACV NPs also have the ExoN motif, dsRNA readily accumulated in infected cells and often colocalized with dsRNA sensors. Moreover, LASV coinfection diminished the accumulation of dsRNA and the IFN response in JUNV-infected cells. The disruption of LASV NP ExoN with a mutation led to dsRNA accumulation and impaired LASV replication in minigenome systems. Importantly, both LASV NP and RNA polymerase L protein were required to diminish the accumulation of dsRNA and the IFN response in JUNV infection. For the first time, we discovered a collaboration between LASV NP ExoN and L protein in limiting dsRNA accumulation. Our new findings provide mechanistic insights into the differential host innate immune responses to highly pathogenic arenavirus infections. IMPORTANCE Arenavirus NPs contain a highly conserved DEDDh ExoN motif, through which LASV NP degrades virus-derived, immunostimulatory dsRNA in biochemical assays to eliminate the danger signal and inhibit the innate immune response. Nevertheless, the function of NP ExoN in arenavirus infection remains to be defined. In this study, we discovered that LASV potently restricts dsRNA accumulation during infection and minigenome replication. In contrast, although the NPs of JUNV and MACV also harbor the ExoN motif, dsRNA readily formed during JUNV and MACV infections, accompanied by IFN and PKR responses. Interestingly, LASV NP alone was not sufficient to limit dsRNA accumulation. Instead, both LASV NP and L protein were required to restrict immunostimulatory dsRNA accumulation. Our findings provide novel and important insights into the mechanism for the distinct innate immune response to these highly pathogenic arenaviruses and open new directions for future studies.

Heterophil cytokine mRNA profiles from genetically distinct lines of chickens with differential heterophil-mediated innate immune responses

2006 ◽  
Vol 35 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Christina L. Swaggerty ◽  
Pete Kaiser ◽  
Lisa Rothwell ◽  
Igal Y. Pevzner ◽  
Michael H. Kogut
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Cytokine Mrna

Evaluating surveillance in wild birds by the application of risk assessment of avian influenza introduction into Spain

2010 ◽  
Vol 139 (1) ◽  
pp. 91-98 ◽  
Author(s):  
M. MARTINEZ ◽  
A. M. PEREZ ◽  
A. DE LA TORRE ◽  
I. IGLESIAS ◽  
J. M. SÁNCHEZ-VIZCAÍNO ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Highly Pathogenic Avian Influenza ◽  
Disease Spread ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
The North ◽  
The Cost ◽  
First Time ◽  
Layer Farm ◽  
H5n1 Hpai

SUMMARYEarly detection of highly pathogenic avian influenza (HPAI) in its natural reservoirs is a prerequisite for preventing disease spread to humans. The risk of introduction of H5N1 HPAI was assessed in order to design a risk-based surveillance system in Spain. Areas at highest risk for H5N1 HPAI followed a northeast–southwest direction, with two significant clusters located in the north and the southwest of the country. Most (83%) of the veterinary units (VUs) obtained fewer samples than would have been expected if samples had been collected using a risk-based design. In October 2009, a HPAI outbreak was reported for the first time in a Spanish layer farm located in a VU at high risk for HPAI, but no samples were collected. This risk-based surveillance approach will increase the cost-effectiveness of HPAI surveillance in Spain and can be easily extended to and adopted by other countries and regions throughout the world.

scholarly journals Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021

2022 ◽  
Author(s):  
Valentina Caliendo ◽  
Nicola S Lewis ◽  
Anne Pohlmann ◽  
Jonas Waldenstrom ◽  
Marielle van Toor ◽  
...  
Keyword(s):  
North America ◽  
Avian Influenza ◽  
Newfoundland And Labrador ◽  
Wild Bird ◽  
Bird Migration ◽  
Highly Pathogenic Avian Influenza ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Influenza H5n1 ◽  
H5n1 Hpai

Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe and Africa, but are currently absent from Oceania and the Americas. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John, Newfoundland and Labrador, Canada. Phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.

scholarly journals Host Innate Immune Response of Geese Infected with Clade 2.3.4.4 H5N6 Highly Pathogenic Avian Influenza Viruses

2020 ◽  
Vol 8 (2) ◽  
pp. 224
Author(s):  
Siyu Wu ◽  
Jianni Huang ◽  
Qiwen Huang ◽  
Junsheng Zhang ◽  
Jing Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Avian Influenza ◽  
Innate Immune Response ◽  
High Mortality ◽  
Highly Pathogenic Avian Influenza ◽  
Southern China ◽  
Influenza Viruses ◽  
Innate Immune ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza

Since 2014, highly pathogenic avian influenza (HPAI) H5N6 viruses have circulated in waterfowls and caused human infections in China, posing significant threats to the poultry industry and the public health. However, the genetics, pathogenicity and innate immune response of H5N6 HPAIVs in geese remain largely unknown. In this study, we analyzed the genetic characteristic of the two H5N6 viruses (GS38 and DK09) isolated from apparently healthy domestic goose and duck in live poultry markets (LPMs) of Southern China in 2016. Phylogenetic analysis showed that the HA genes of the two H5N6 viruses belonged to clade 2.3.4.4 and were clustered into the MIX-like group. The MIX-like group viruses have circulated in regions such as China, Japan, Korea, and Vietnam. The NA genes of the two H5N6 viruses were classified into the Eurasian sublineage. The internal genes including PB2, PB1, PA, NP, M, and NS of the two H5N6 viruses derived from the MIX-like. Therefore, our results suggested that the two H5N6 viruses were reassortants of the H5N1 and H6N6 viruses and likely derived from the same ancestor. Additionally, we evaluated the pathogenicity and transmission of the two H5N6 viruses in domestic geese. Results showed that both the two viruses caused serious clinical symptoms in all inoculated geese and led to high mortality in these birds. Both the two viruses were transmitted efficiently to contact geese and caused lethal infection in these birds. Furthermore, we found that mRNA of pattern recognition receptors (PRRs), interferons (IFNs), and stimulated genes (ISGs) exhibited different levels of activation in the lungs and spleens of the two H5N6 viruses-inoculated geese though did not protect these birds from H5N6 HPAIVs infection. Our results suggested that the clade 2.3.4.4 waterfowl-origin H5N6 HPAIVs isolated from LPMs of Southern China could cause high mortality in geese and innate immune-related genes were involved in the geese innate immune response to H5N6 HPAIVs infection. Therefore, we should pay more attention to the evolution, pathogenic variations of these viruses and enhance virological surveillance of clade 2.3.4.4 H5N6 HPAIVs in waterfowls in China.

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