Host immune responses of ducks infected with H5N1 highly pathogenic avian influenza viruses of different pathogenicities

Wei, Liangmeng; Jiao, Peirong; Song, Yafen; Cao, Lingfeng; Yuan, Runyu; Gong, Lang; Cui, Jin; Zhang, Shuo; Qi, Wenbao; Yang, Shuxu; Liao, Ming

doi:10.1016/j.vetmic.2013.06.019

Cited by 36 publications

(43 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, disease severity and high fatality rates reported in humans have been associated with virus-induced cytokine dysregulation and hyperactive inflammatory responses in the host (5-7). A positive correlation between cytokine levels and virus pathogenicity has also been observed in ducks (38) and chickens (39) infected with HPAI H5N1. Our data clearly demonstrate that HPAI H5N1 consistently stimulates more cytokine production (especially IL-6, IFN-␤, and CXCL10) than low pathogenic influenza viruses in various cell lines.…”

Section: Discussionmentioning

confidence: 71%

Inhibition of Reactive Oxygen Species Production Ameliorates Inflammation Induced by Influenza A Viruses via Upregulation of SOCS1 and SOCS3

Lowther

Stambas

2015

J Virol

View full text Add to dashboard Cite

Highly pathogenic avian influenza virus infection is associated with severe mortality in both humans and poultry. The mechanisms of disease pathogenesis and immunity are poorly understood although recent evidence suggests that cytokine/chemokine dysregulation contributes to disease severity following H5N1 infection. Influenza A virus infection causes a rapid influx of inflammatory cells, resulting in increased reactive oxygen species production, cytokine expression, and acute lung injury. Proinflammatory stimuli are known to induce intracellular reactive oxygen species by activating NADPH oxidase activity. We therefore hypothesized that inhibition of this activity would restore host cytokine homeostasis following avian influenza virus infection. A panel of airway epithelial and immune cells from mammalian and avian species were infected with A/Puerto Rico/8/ 1934 H1N1 virus, low-pathogenicity avian influenza H5N3 virus (A/duck/Victoria/0305-2/2012), highly pathogenic avian influenza H5N1 virus (A/chicken/Vietnam/0008/2004), or low-pathogenicity avian influenza H7N9 virus (A/Anhui/1/2013). Quantitative real-time reverse transcriptase PCR showed that H5N1 and H7N9 viruses significantly stimulated cytokine (interleukin-6, beta interferon, CXCL10, and CCL5) production. Among the influenza-induced cytokines, CCL5 was identified as a potential marker for overactive immunity. Apocynin, a Nox2 inhibitor, inhibited influenza-induced cytokines and reactive oxygen species production, although viral replication was not significantly altered in vitro. Interestingly, apocynin treatment significantly increased influenza virus-induced mRNA and protein expression of SOCS1 and SOCS3, enhancing negative regulation of cytokine signaling. These findings suggest that apocynin or its derivatives (targeting host responses) could be used in combination with antiviral strategies (targeting viruses) as therapeutic agents to ameliorate disease severity in susceptible species. IMPORTANCEHighly pathogenic avian influenza virus infection causes severe morbidity and mortality in both humans and poultry. Widespread antiviral resistance necessitates the need for the development of additional novel therapeutic measures to modulate overactive host immune responses after infection. Disease severity following avian influenza virus infection can be attributed in part to hyperinduction of inflammatory mediators such as cytokines, chemokines, and reactive oxygen species. Our study shows that highly pathogenic avian influenza H5N1 virus and low-pathogenicity avian influenza H7N9 virus (both associated with human fatalities) promote inactivation of FoxO3 and downregulation of the TAM receptor tyrosine kinase, Tyro3, leading to augmentation of the inflammatory cytokine response. Inhibition of influenza-induced reactive oxygen species with apocynin activated FoxO3 and stimulated SOCS1 and SOCS3 proteins, restoring cytokine homeostasis. We conclude that modulation of host immune responses with antioxidant and/or anti-inflammatory agents in combinati...

show abstract

Section: Discussionmentioning

confidence: 71%

Inhibition of Reactive Oxygen Species Production Ameliorates Inflammation Induced by Influenza A Viruses via Upregulation of SOCS1 and SOCS3

Lowther

Stambas

2015

J Virol

View full text Add to dashboard Cite

show abstract

“…The analysis of transcripts in the liver revealed that the expression levels of inflammatory cytokines (e.g., IL-2, IL-6) and chemokines (e.g., IL-8) in Z8S2 were significantly higher than those in Z8R2, suggesting that susceptible Z8S2 Pekin ducks exhibits a much stronger inflammatory response than resistant Z8R2. Previous works have shown that highly pathogenic avian influenza viruses cause strongly elevated levels of cytokines and chemokines in mammals and birds, resulting in detrimental immune pathologies and tissue damage (Srivastava et al, 2009; Suzuki et al, 2009; Wei et al, 2013; Burggraaf et al, 2014; Oldstone and Rosen, 2014). It is likely that the severe liver pathology and high mortality in Z8S2 ducks may be correlated with the strong innate immune response and inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Host Differences Affecting Resistance and Susceptibility of the Second Generation of a Pekin Duck Flock to Duck Hepatitis A Virus Genotype 3

et al. 2017

View full text Add to dashboard Cite

Earlier work suggested the possibility to anti duck hepatitis A virus genotype 3 (DHAV-3) using the resistance breeding strategy. Here, we report the creation of the second generations of a resistant Pekin duck flock (designated Z8R2) and a highly susceptible Pekin duck flock (designated Z8S2) and the investigation of their responses to DHAV-3. Experimental infection with DHAV-3 at 7 days of age resulted in a high mortality (66.3%) in 11 susceptible Z8S2 families and an extremely low mortality rate (2.67%) in 32 Z8R2 families, indicating that Z8R2 exhibits strong resistance to DHAV-3, while Z8S2 is highly susceptible to the virus. Detection of DHAV-3 in the liver between 1 and 60 hours post inoculation (hpi) suggests that DHAV-3 can be replicated rapidly and efficiently in the liver of Z8S2, whereas the replication of the virus in the liver of Z8R2 is suppressed greatly. High levels of serum biochemical markers (e.g., ALT, AST, ALP and GGT) were detected in Z8S2 at 24 hpi, which were significantly higher than those in Z8R2. Analysis of transcripts in the liver revealed that the expression levels of several pattern recognition receptors (PRRs) (e.g., TLR4/7, RIG-1 and MDA5) and cytokines (e.g., IL-2, IL-6, IL-8, IFN-α, and IFN-γ) in Z8S2 were significantly higher than those in Z8R2 at 12 and 24 hpi. Together these findings suggest that Z8R2 and Z8S2 Pekin ducks, which were derived from the same Z8 line, exhibit disparate pathogenic outcomes following DHAV-3 infection. Therefore, it is possible to select a Pekin duck flock resistant to DHAV-3 employing the strategy described here. It is likely that the high viral load and the strong inflammatory response correlate with the high susceptibility of Z8S2 Pekin ducks to DHAV-3.

show abstract

“…Such results suggest that the engagement of the TLRs and cytokines are involved in a tissue-dependent manner. Previous studies have revealed tissue-specific immune responses following infection with H5N1 (Wei et al, 2013), H5N2 (Vanderven et al, 2012), and H7N1 (Cornelissen et al, 2012). The difference of cell types could be associated with immune responses and virus titers in the tissues tested for infection.…”

Section: Discussionmentioning

confidence: 99%

Immune Responses of Chickens Infected with Wild Bird-Origin H5N6 Avian Influenza Virus

et al. 2017

Self Cite

View full text Add to dashboard Cite

Since April 2014, new infections of H5N6 avian influenza virus (AIV) in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283) in Pallas’s sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015), whereas a virus (i.e., SW8) isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6). However, the pathogenicity, transmissibility, and host immune-related response of chickens infected by those wild bird-origin H5N6 AIVs remain unknown. In response, we examined the viral distribution and mRNA expression profiles of immune-related genes in chickens infected with both viruses. Results showed that the H5N6 AIVs were highly pathogenic to chickens and caused not only systemic infection in multiple tissues, but also 100% mortality within 3–5 days post-infection. Additionally, ZH283 efficiently replicated in all tested tissues and transmitted among chickens more rapidly than SW8. Moreover, quantitative real-time polymerase chain reaction analysis showed that following infection with H5N6, AIVs immune-related genes remained active in a tissue-dependent manner, as well as that ZH283 induced mRNA expression profiles such as TLR3, TLR7, IL-6, TNF-α, IL-1β, IL-10, IL-8, and MHC-II to a greater extent than SW8 in the tested tissues of infected chickens. Altogether, our findings help to illuminate the pathogenesis and immunologic mechanisms of H5N6 AIVs in chickens.

show abstract

Host immune responses of ducks infected with H5N1 highly pathogenic avian influenza viruses of different pathogenicities

Cited by 36 publications

References 41 publications

Inhibition of Reactive Oxygen Species Production Ameliorates Inflammation Induced by Influenza A Viruses via Upregulation of SOCS1 and SOCS3

Inhibition of Reactive Oxygen Species Production Ameliorates Inflammation Induced by Influenza A Viruses via Upregulation of SOCS1 and SOCS3

Host Differences Affecting Resistance and Susceptibility of the Second Generation of a Pekin Duck Flock to Duck Hepatitis A Virus Genotype 3

Immune Responses of Chickens Infected with Wild Bird-Origin H5N6 Avian Influenza Virus

Contact Info

Product

Resources

About