Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Virology Journal
Published in: Virology Journal 1/2018

Open Access 01-12-2018 | Research

Potential mediators of in ovo delivered double stranded (ds) RNA-induced innate response against low pathogenic avian influenza virus infection

Authors: Hanaa Ahmed-Hassan, Mohamed Sarjoon Abdul-Cader, Upasama De Silva Senapathi, Maha Ahmed Sabry, Eman Hamza, Eva Nagy, Shayan Sharif, Mohamed Faizal Abdul-Careem

Published in: Virology Journal | Issue 1/2018

Login to get access

Abstract

Background

Toll like receptor (TLR) 3 is a critically important innate pattern recognizing receptor that senses many viral infections. Although, it has been shown that double stranded (ds) RNA can be used for the stimulation of TLR3 signaling pathway in a number of host-viral infection models, it’s effectiveness as an antiviral agent against low pathogenic avian influenza virus (LPAIV) needs further investigation.

Methods

In this study, first, we delivered TLR3 ligand, dsRNA, in ovo at embryo day (ED)18 since in ovo route is routinely used for vaccination against poultry viral and parasitic infections and infected with H4N6 LPAIV 24-h post-treatment. A subset of in ovo dsRNA treated and control groups were observed for the expressions of TLR3 and type I interferon (IFN)s, mRNA expression of interleukin (IL)-1β and macrophage recruitment coinciding with the time of H4N6 LPAIV infection (24 h post-treatment). Additionally, Day 1 chickens were given dsRNA intra-tracheally along with a control group and a subset of chickens were infected with H4N6 LPAIV 24-h post-treatment whereas the rest of the animals were observed for macrophage and type 1 IFN responses coinciding with the time of viral infection.

Results

Our results demonstrate that the pre-hatch treatment of eggs with dsRNA reduces H4N6 replication in lungs. Further studies revealed that in ovo delivery of dsRNA increases TLR3 expression, type I IFN production and number of macrophages in addition to mRNA expression of IL-1β in lung 24-h post-treatment. The same level of induction of innate response was not evident in the spleen. Moreover, we discovered that dsRNA elicits antiviral response against LPAIV correlating with type I IFN activity in macrophages in vitro. Post-hatch, we found no difference in H4N6 LPAIV genome loads between dsRNA treated and control chickens although we observed higher macrophage recruitment and IFN-β response coinciding with the time of viral infection.

Conclusions

Our findings imply that the TLR3 ligand, dsRNA has antiviral activity in ovo and in vitro but not in chickens post-hatch and dsRNA-mediated innate host response is characterized by macrophage recruitment and expressions of TLR3 and type 1 IFNs.
Literature
1.
Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza a viruses. Microbiol Rev. 1992;56:152–79.PubMedPubMedCentral
2.
3.
Mumford E, Bishop J, Hendrickx S, Embarek PB, Perdue M. Avian influenza H5N1: risks at the human-animal interface. Food Nutr Bull. 2007;28:S357–63.CrossRefPubMed
4.
Chen J, Chen SC, Stern P, Scott BB, Lois C. Genetic strategy to prevent influenza virus infections in animals. J Infect Dis. 2008;197(Suppl 1):S25–8.CrossRefPubMedPubMedCentral
5.
Yee KS, Carpenter TE, Cardona CJ. Epidemiology of H5N1 avian influenza. Comp Immunol Microbiol Infect Dis. 2009;32:325–40.CrossRefPubMed
6.
Capua I, Alexander DJ. The challenge of avian influenza to the veterinary community. Avian Pathol. 2006;35:189–205.CrossRefPubMed
7.
Swayne DE, Pavade G, Hamilton K, Vallat B, Miyagishima K. Assessment of national strategies for control of high-pathogenicity avian influenza and low-pathogenicity notifiable avian influenza in poultry, with emphasis on vaccines and vaccination. Rev Sci Tech. 2011;30:839–70.CrossRefPubMed
8.
Savill NJ, St Rose SG, Keeling MJ, Woolhouse ME. Silent spread of H5N1 in vaccinated poultry. Nature. 2006;442:757.CrossRefPubMed
9.
Capua I, Alexander DJ. Ecology, epidemiology and human health implications of avian influenza viruses: why do we need to share genetic data? Zoonoses Public Health. 2008;55:2–15.CrossRefPubMed
10.
Hafez MH, Arafa A, Abdelwhab EM, Selim A, Khoulosy SG, Hassan MK, Aly MM. Avian influenza H5N1 virus infections in vaccinated commercial and backyard poultry in Egypt. Poult Sci. 2010;89:1609–13.CrossRefPubMed
11.
Abdelwhab EM, Hafez HM. Insight into alternative approaches for control of avian influenza in poultry, with emphasis on highly pathogenic H5N1. Viruses. 2012;4:3179–208.CrossRefPubMedPubMedCentral
12.
Mehta DR, Ashkar AA, Mossman KL. The nitric oxide pathway provides innate antiviral protection in conjunction with the type I interferon pathway in fibroblasts. PLoS One. 2012;7:e31688.CrossRefPubMedPubMedCentral
13.
Weber F, Wagner V, Rasmussen SB, Hartmann R, Paludan SR. Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J Virol. 2006;80:5059–64.CrossRefPubMedPubMedCentral
14.
Leaman DW, Chawla-Sarkar M, Jacobs B, Vyas K, Sun Y, Ozdemir A, Yi T, Williams BR, Borden EC. Novel growth and death related interferon-stimulated genes (ISGs) in melanoma: greater potency of IFN-beta compared with IFN-alpha2. J Interf Cytokine Res. 2003;23:745–56.CrossRef
15.
Lakhdari O, McAllister CS, Wang M, Minev I, Prince LS, Eckmann L, Kagnoff MF. TLR3 signaling is downregulated by a MAVS isoform in epithelial cells. Cell Immunol. 2016;310:205–10.CrossRefPubMedPubMedCentral
16.
Cleary CM, Donnelly RJ, Soh J, Mariano TM, Pestka S. Knockout and reconstitution of a functional human type I interferon receptor complex. J Biol Chem. 1994;269:18747–9.PubMed
17.
Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, Colamonici OR. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem. 1995;270:21606–11.CrossRefPubMed
18.
Soh J, Mariano TM, Lim JK, Izotova L, Mirochnitchenko O, Schwartz B, Langer JA, Pestka S. Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening. J Biol Chem. 1994;269:18102–10.PubMed
19.
Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem. 2007;282:20059–63.CrossRefPubMed
20.
Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011;472:481–5.CrossRefPubMedPubMedCentral
21.
de Veer MJ, Holko M, Frevel M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR. Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol. 2001;69:912–20.PubMed
22.
Cheng J, Sun Y, Zhang X, Zhang F, Zhang S, Yu S, Qiu X, Tan L, Song C, Gao S, et al. Toll-like receptor 3 inhibits Newcastle disease virus replication through activation of pro-inflammatory cytokines and the type-1 interferon pathway. Arch Virol. 2014;159:2937–48.CrossRefPubMed
23.
Hu X, Zou H, Qin A, Qian K, Shao H, Ye J. Activation of toll-like receptor 3 inhibits Marek's disease virus infection in chicken embryo fibroblast cells. Arch Virol. 2016;161:521–8.CrossRefPubMed
24.
Zou H, Su R, Ruan J, Shao H, Qian K, Ye J, Qin A. Toll-like receptor 3 pathway restricts Marek's disease virus infection. Oncotarget. 2017;8:70847–53.PubMedPubMedCentral
25.
St Paul M, Mallick AI, Read LR, Villanueva AI, Parvizi P, Abdul-Careem MF, Nagy E, Sharif S. Prophylactic treatment with toll-like receptor ligands enhances host immunity to avian influenza virus in chickens. Vaccine. 2012;30:4524–31.CrossRefPubMed
26.
Abdul-Cader MS, Palomino-Tapia V, Amarasinghe A, Ahmed-Hassan H, De Silva SU, Abdul-Careem MF. Hatchery vaccination against poultry viral diseases: potential mechanisms and limitations. Viral Immunol. 2018;31:23–33.
27.
Qureshi MA, Miller L, Lillehoj HS, Ficken MD. Establishment and characterization of a chicken mononuclear cell line. Vet Immunol Immunopathol. 1990;26:237–50.CrossRefPubMed
28.
Abdul-Cader MS, Ahmed-Hassan H, Amarasinghe A, Nagy E, Sharif S, Abdul-Careem MF. Toll-like receptor (TLR)21 signalling-mediated antiviral response against avian influenza virus infection correlates with macrophage recruitment and nitric oxide production. J Gen Virol. 2017;98:1209–23.CrossRefPubMed
29.
Abdul-Careem MF, Hunter BD, Sarson AJ, Mayameei A, Zhou H, Sharif S. Marek's disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system. Viral Immunol. 2006;19:167–76.CrossRefPubMed
30.
Villanueva AI, Kulkarni RR, Sharif S. Synthetic double-stranded RNA oligonucleotides are immunostimulatory for chicken spleen cells. Dev Comp Immunol. 2011;35:28–34.CrossRefPubMed
31.
32.
Zhang Z, Zou T, Hu X, Jin H. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts. Mol Immunol. 2015;68:657–62.CrossRefPubMed
33.
Barjesteh N, Behboudi S, Brisbin JT, Villanueva AI, Nagy E, Sharif S. TLR ligands induce antiviral responses in chicken macrophages. PLoS One. 2014;9:e105713.CrossRefPubMedPubMedCentral
34.
Kramer MJ, Dennin R, Kramer C, Jones G, Connell E, Rolon N, Gruarin A, Kale R, Trown PW. Cell and virus sensitivity studies with recombinant human alpha interferons. J Interf Res. 1983;3:425–35.CrossRef
35.
Vogel SN, Fertsch D. Macrophages from endotoxin-hyporesponsive (Lpsd) C3H/HeJ mice are permissive for vesicular stomatitis virus because of reduced levels of endogenous interferon: possible mechanism for natural resistance to virus infection. J Virol. 1987;61:812–8.PubMedPubMedCentral
36.
Sharma JM, Burmester BR. Resistance to Marek's disease at hatching in chickens vaccinated as embryos with the Turkey herpesvirus. Avian Dis. 1982;26:134–49.CrossRefPubMed
37.
Gomis S, Babiuk L, Allan B, Willson P, Waters E, Ambrose N, Hecker R, Potter A. Protection of neonatal chicks against a lethal challenge of Escherichia coli using DNA containing cytosine-phosphodiester-guanine motifs. Avian Dis. 2004;48:813–22.CrossRefPubMed
38.
Taghavi A, Allan B, Mutwiri G, Van Kessel A, Willson P, Babiuk L, Potter A, Gomis S. Protection of neonatal broiler chicks against salmonella typhimurium septicemia by DNA containing CpG motifs. Avian Dis. 2008;52:398–406.CrossRefPubMed
39.
Thapa S, Cader MS, Murugananthan K, Nagy E, Sharif S, Czub M, Abdul-Careem MF. In ovo delivery of CpG DNA reduces avian infectious laryngotracheitis virus induced mortality and morbidity. Viruses. 2015;7:1832–52.CrossRefPubMedPubMedCentral
40.
Dar A, Potter A, Tikoo S, Gerdts V, Lai K, Babiuk LA, Mutwiri G. CpG oligodeoxynucleotides activate innate immune response that suppresses infectious bronchitis virus replication in chicken embryos. Avian Dis. 2009;53:261–7.CrossRefPubMed
41.
Ashkar AA, Yao XD, Gill N, Sajic D, Patrick AJ, Rosenthal KL. Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA. J Infect Dis. 2004;190:1841–9.CrossRefPubMed
42.
Wong JP, Christopher ME, Viswanathan S, Karpoff N, Dai X, Das D, Sun LQ, Wang M, Salazar AM. Activation of toll-like receptor signaling pathway for protection against influenza virus infection. Vaccine. 2009;27:3481–3.CrossRefPubMed
43.
Sharma JM. In situ production of interferon in tissues of chickens exposed as embryos to Turkey herpesvirus and Marek's disease virus. Am J Vet Res. 1989;50:882–6.PubMed
44.
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature. 2001;413:732–8.CrossRefPubMed
45.
Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med. 2008;205:1601–10.CrossRefPubMedPubMedCentral
46.
Karpala AJ, Lowenthal JW, Bean AG. Activation of the TLR3 pathway regulates IFNbeta production in chickens. Dev Comp Immunol. 2008;32:435–44.CrossRefPubMed
47.
Karpala AJ, Stewart C, McKay J, Lowenthal JW, Bean AG. Characterization of chicken Mda5 activity: regulation of IFN-beta in the absence of RIG-I functionality. J Immunol. 2011;186:5397–405.CrossRefPubMed
48.
Barber MR, Aldridge JR Jr, Webster RG, Magor KE. Association of RIG-I with innate immunity of ducks to influenza. Proc Natl Acad Sci U S A. 2010;107:5913–8.CrossRefPubMedPubMedCentral
49.
Palchetti S, Starace D, De Cesaris P, Filippini A, Ziparo E, Riccioli A. Transfected poly(I:C) activates different dsRNA receptors, leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells. J Biol Chem. 2015;290:5470–83.CrossRefPubMedPubMedCentral
50.
Kumar MV, Nagineni CN, Chin MS, Hooks JJ, Detrick B. Innate immunity in the retina: toll-like receptor (TLR) signaling in human retinal pigment epithelial cells. J Neuroimmunol. 2004;153:7–15.CrossRefPubMed
51.
Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol. 2004;31:358–64.CrossRefPubMed
52.
Kang Y, Feng M, Zhao X, Dai X, Xiang B, Gao P, Li Y, Li Y, Ren T. Newcastle disease virus infection in chicken embryonic fibroblasts but not duck embryonic fibroblasts is associated with elevated host innate immune response. Virol J. 2016;13:41.CrossRefPubMedPubMedCentral
53.
Haunshi S, Cheng HH. Differential expression of toll-like receptor pathway genes in chicken embryo fibroblasts from chickens resistant and susceptible to Marek's disease. Poult Sci. 2014;93:550–5.CrossRefPubMed
54.
Hayashi T, Watanabe C, Suzuki Y, Tanikawa T, Uchida Y, Saito T. Chicken MDA5 senses short double-stranded RNA with implications for antiviral response against avian influenza viruses in chicken. J Innate Immun. 2014;6:58–71.CrossRefPubMed
55.
Stowell NC, Seideman J, Raymond HA, Smalley KA, Lamb RJ, Egenolf DD, Bugelski PJ, Murray LA, Marsters PA, Bunting RA, et al. Long-term activation of TLR3 by poly(I:C) induces inflammation and impairs lung function in mice. Respir Res. 2009;10:43.CrossRefPubMedPubMedCentral
56.
57.
Schneider C, Nobs SP, Heer AK, Kurrer M, Klinke G, van Rooijen N, Vogel J, Kopf M. Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection. PLoS Pathog. 2014;10:e1004053.CrossRefPubMedPubMedCentral
58.
Ghoneim HE, Thomas PG, McCullers JA. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol. 2013;191:1250–9.CrossRefPubMedPubMedCentral
59.
Hu W, Jain A, Gao Y, Dozmorov IM, Mandraju R, Wakeland EK, Pasare C. Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation. Proc Natl Acad Sci U S A. 2015;112:13994–9.CrossRefPubMedPubMedCentral
60.
Mo CW, Cao YC, Lim BL. The in vivo and in vitro effects of chicken interferon alpha on infectious bursal disease virus and Newcastle disease virus infection. Avian Dis. 2001;45:389–99.CrossRefPubMed
61.
Pei J, Sekellick MJ, Marcus PI, Choi IS, Collisson EW. Chicken interferon type I inhibits infectious bronchitis virus replication and associated respiratory illness. J Interf Cytokine Res. 2001;21:1071–7.CrossRef
62.
Jarosinski KW, Jia W, Sekellick MJ, Marcus PI, Schat KA. Cellular responses in chickens treated with IFN-alpha orally or inoculated with recombinant Marek's disease virus expressing IFN-alpha. J Interf Cytokine Res. 2001;21:287–96.CrossRef
63.
Meng S, Yang L, Xu C, Qin Z, Xu H, Wang Y, Sun L, Liu W. Recombinant chicken interferon-alpha inhibits H9N2 avian influenza virus replication in vivo by oral administration. J Interf Cytokine Res. 2011;31:533–8.CrossRef
64.
Haasbach E, Droebner K, Vogel AB, Planz O. Low-dose interferon type I treatment is effective against H5N1 and swine-origin H1N1 influenza a viruses in vitro and in vivo. J Interf Cytokine Res. 2011;31:515–25.CrossRef
65.
St Hill CA, Sharma JM. Response of embryonic chicken lymphocytes to in ovo exposure to lymphotropic viruses. Am J Vet Res. 1999;60:937–41.PubMed
66.
Umar S, Guerin JL, Ducatez MF. Low pathogenic avian influenza and Coinfecting pathogens: a review of experimental infections in avian models. Avian Dis. 2017;61:3–15.CrossRefPubMed
Metadata
Title
Potential mediators of in ovo delivered double stranded (ds) RNA-induced innate response against low pathogenic avian influenza virus infection
Authors
Hanaa Ahmed-Hassan
Mohamed Sarjoon Abdul-Cader
Upasama De Silva Senapathi
Maha Ahmed Sabry
Eman Hamza
Eva Nagy
Shayan Sharif
Mohamed Faizal Abdul-Careem
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2018
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-018-0954-2

Other articles of this Issue 1/2018

Virology Journal 1/2018 Go to the issue

Research

Human papillomavirus type 16 E6 and E7 oncoproteins interact with the nuclear p53-binding protein 1 in an in vitro reconstructed 3D epithelium: new insights for the virus-induced DNA damage response

Research

Ebolavirus diagnosis made simple, comparable and faster than molecular detection methods: preparing for the future

Research

Metagenomic analysis of viruses associated with maize lethal necrosis in Kenya

Research

Detection and genetic characterization of feline bocavirus in Northeast China

Research

Duck enteritis virus activates CaMKKβ-AMPK to trigger autophagy in duck embryo fibroblast cells via increased cytosolic calcium

Research

Intra-epidemic genome variation in highly pathogenic African swine fever virus (ASFV) from the country of Georgia

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits