UK-China partnership on Global Food Security: Combating avian tumor diseases for sustainable poultry production

Lead Research Organisation: The Pirbright Institute
Department Name: Avian Oncogenic Viruses

Abstract

Infectious diseases result in direct and indirect losses at various steps of poultry farming and amongst them neoplastic disease caused by viruses is a major economic problem faced by the poultry industry worldwide. The oncogenic viruses causing neoplastic infection in chickens are herpesviruses comprising of Marek's disease virus (MDV) and retroviruses comprising of reticuloendotheliosis virus (REV) and avian leucosis virus (ALV). ALV is the most common naturally occurring avian retrovirus that can cause a variety of neoplastic disease conditions in chickens. In addition to causing neoplasia, ALV is known to be associated with reduced productivity and other production problems in affected flocks. Based on the properties of viral envelope glycoproteins, ALV is classified into six subgroups: A, B, C, D, E and J. Originally isolated by the Pirbright Institute in the late 1980s, ALV-J spreads widely and induces myeloid leukosis and a broad spectrum of additional disorders, such as histiocytic sarcoma, hemangiomas and erythroblastosis. The original strains have almost been eradicated from most of the commercial poultry flocks in Europe and the United States but in Asia, the virus evolved into a great variety and recently emerging Chinese isolates coarsely induce various tumours in both commercial laying hen flocks as well as native Chinese breeds of chickens. Defining the molecular background of the tumorigenesisis is needed to develop more effective control and eradication programmes in China. In this proposal, we aim to obtain detailed comprehensive picture on the molecular events to understand and predict the molecular pathways to ALV-J induced cancer. This includes non-coding RNA profiling for the role of non-coding RNAs in ALV-J induced oncogenesis, oncogene myc targetome identification and the role of myc-binding in maintaining the transformed phenotype and myc knockout by CRISPR/Cas9 system for the role of myc in maintaining the transformed phenotype. As the co-infection of ALV-J with other tumor viruses such as Marek's disease virus and Reticuloendotheliosis virus is very common and caused more serious pathogenic effects, we are going to elucidate the synergistic mechanism of ALV-J+REV/ALV-J+MDV co-infection in vitro and in vivo. The findings will be very valuable in developing new approaches for the eradication of ALV-J in China and control of cancers caused by oncogenic viruses. We also want to establish the resistant cell line by editing ALV-J receptor NHE1 using CRISPR/Cas9 system to explore genetic resistant to ALV-J. Finally, we will develop the rapid diagnostic kits to detect ALV-J infection in the field to aid the ALV-J control and eradication in China.

Planned Impact

Poultry industry is a rapidly growing sector crucial for the global food security, acting as a major source of protein for the growing world population. Avian leukosis viruses (ALV) are retroviruses associated with the induction of tumours of haemopoietic cells in birds. Although diseases due to ALV have largely been controlled in Europe and USA through successful eradication programmes, it continues to be a major problem in many countries including China, where it has caused serious economic losses in recent years. In particular, myeloid leukosis and other tumours due to ALV-J remains a major disease that threatens the Chinese poultry industry. Detailed understanding of the molecular basis of tumours induced by ALV-J, generation of resistant cell line, and development of rapid diagnostic tools for ALV-J detection in the field all will benefit development of new strategies for control and eradication of ALV-J in Chinese poultry industry. The beneficiaries of this research will include academic scientists, the poultry breeding companies, chicken farms, diagnostic professionals, the Pirbright Institute, the BBSRC and its stakeholders such as Defra and the UK poultry farming industry.
The research will have general impact with the wider scientific community, veterinary and medical practitioners, students and general public. Engagement with these diverse groups will be achieved via meetings, articles in the trade press, tailored web pages, press releases to the media and outreach events in schools.
In the longer term the research may lead to medical benefits by improving control of human virus pathogens which will benefit the UK MRC and UK department of Health, the pharmaceutical industry and international organization such as the World Health Organization.
If the proposed studies lead to new approaches for controlling ALV-J or other viral diseases, additional funding will be sought from relevant funding agencies and other sources for further development. There is extensive experience within the Pirbright Institute of patent applications and commercialisations, new opportunities will feed into an established system for technology development and knowledge transfer by the Pirbright Business Development group.
Rapid-onset transformation induced by myc is also a good model for studying cancers in other species including humans as myc is one of the most frequently deregulated oncogenes in human malignancies.

Publications

10 25 50

 
Description In situ CRISPR/Cas9 gene editing tools for functional genomics in ALV-transformed cell lines: ALV is a typical retrovirus which induces the pathogenicity by integration into the host genome. After integration, LTR acts as promoter to activate the expression of the oncogene and induce tumors. The development of lymphoid leukosis is a result of cooperation of c-Myc and c-Bic (encoding the oncogenic miRNA mir-155) integration and activation by ALV. Using the CRISPR/Cas9 editing system, we have shown that both LTR and c-Myc but not miR-155 are essential for the continued proliferation of ALV transformed B cell line HP45.
The role of c-Myc oncogene in regulating the transcriptional machinery of ALV transformed cells: c-Myc is a transcription factor that binds to specific signature sequences in the different promoters in regulating expression. To examine the role of Myc in ALV-induced transformation, we determined the global Myc-binding sites in the genome of ALV cell line HP45 using Myc-ChIP (chromatin immunoprecipitation) analysis after tagging c-Myc with AM tag which has got a good Chippable antibody. After the ChIP-seq assay, a complete data set of the myc binding sites in the whole genome of HP45 was obtained.
Speci?c high-sensitivity enzymatic reporter unlocking (SHERLOCK) platform for diagnosis of ALV: As vaccines are not available for ALV, the current practice of eradication involves early detection and removal of infected birds to reduce contact and the incidence of horizontal spread. To aid the eradication program, rapid, sensitive, specific, easy-to-use and cost effective on-site diagnostic method is needed. We have developed a lateral flow detection method using Cas13a-based SHERLOCK platform for rapid detection of the most common ALV subgroups A, B, and J.
Exploitation Route Establishment of the pipeline for in situ CRISPR editing of lymphoma-derived cell lines, gives the opportunity for the identification of critical viral and host genes involved in features such as virus-host interactions, neoplastic transformation, and virus latency.
Determination of the global myc-binding profiles in transformed macrophages could provide insights into its role in transformation.
Achieving rapid detection of ALV infection is imperative in effective control of the spread of ALVs.
Sectors Agriculture

Food and Drink

 
Description By working with the Chinese partners, various innovative research findings have been used to secure additional joint research funds on areas such as virus pathogenesis, host-virus interactions and virus persistence in diseases such as Marek's disease and avian leukosis. We have won 4 joint grants, published over 20 joint research papers, organised 3 conferences and supported 4 exchange visits. Translation of the research outputs include the development of improved diagnostics and innovative vaccines against avian diseases. Some of the novel recombinant vaccines against avian diseases are currently being evaluated for commercial use to protect against major avian diseases.
First Year Of Impact 2017
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description BBSRC IAA The Pirbright Institute
Amount £300,000 (GBP)
Funding ID BB/S506680/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2018 
End 03/2021
 
Description CRISPR/Cas system-based molecular diagnostics for avian viral pathogens
Amount £21,263 (GBP)
Organisation The Pirbright Institute 
Sector Academic/University
Country United Kingdom
Start 01/2020 
End 03/2020
 
Description Collaborative partnership for establish of PhysioMimix™ OOC system, part of Pirbright Institute Flexible Talent Mobility Account
Amount £180,000 (GBP)
Funding ID BB/S507945/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2020 
End 12/2020
 
Description Development of HVT vectored vaccine
Amount £100,000 (GBP)
Organisation MSD Animal Health 
Sector Private
Country United Kingdom
Start 11/2022 
End 04/2023
 
Description Development of an HVT triple insert vaccine using CRISPR/Cas9 technology and novel vector vaccines
Amount £140,000 (GBP)
Organisation MSD Animal Health 
Sector Private
Country United Kingdom
Start 02/2019 
End 01/2020
 
Description International Exchanges 2021 Cost Share (NSFC)
Amount £12,000 (GBP)
Funding ID IEC\NSFC\211090 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2022 
End 03/2024
 
Title Lateral flow detection of avian leukosis viruses and Reticuloendotheliosis virus 
Description The system for detecting ALV/REV based on CRISPR-Cas13a, a SHERLOCK reaction system consists of specific RPA primers for amplifying target nucleic acid fragments, Cas13a protein, crRNA, and Lateral flow chromatography test strip for visualized display of results. The assay started with pre-amplification of either a DNA or RNA target input. Amplified targets are then converted to RNA via T7 transcription and detected by Cas13-crRNA complexes, which activate and cleave fluorescent RNA reporters based on its collateral cleavage nature. The result can be visualized using colorimetric lateral flow reaction. The test is rapid, sensitive and specific for detection of ALV/REV at 37°C. The product can commercialized with a great clinical application prospects. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? No  
Impact The early identi?cation and removal of virus-shedding birds are essential to reduce the transmission. This rapid, simple-to-use and cost effective on-site diagnostic method will aid the eradication of ALV/REV in the affected area. 
 
Title MOESM1 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 1. The potential miRNA targets of the differentially expressed miRNA between ExoRJ and ExoJ. Numerous target genes, 19,450 for 54 miRNAs, were predicted as potential miRNA targets. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM1_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM1 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 1. The potential miRNA targets of the differentially expressed miRNA between ExoRJ and ExoJ. Numerous target genes, 19,450 for 54 miRNAs, were predicted as potential miRNA targets. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM1_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM2 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 2. The potential miRNA targets of the differentially expressed miRNA between ExoRJ and ExoR. Numerous target genes, 6058 for 16 miRNAs, were predicted as potential miRNA targets. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM2_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM2 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 2. The potential miRNA targets of the differentially expressed miRNA between ExoRJ and ExoR. Numerous target genes, 6058 for 16 miRNAs, were predicted as potential miRNA targets. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM2_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM3 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 3. The GO annotation of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoJ. A GO annotation of the predicted target genes revealed that 100 target genes were annotated significantly for the 54 differentially expressed miRNAs between ExoRJ and ExoJ. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM3_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM3 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 3. The GO annotation of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoJ. A GO annotation of the predicted target genes revealed that 100 target genes were annotated significantly for the 54 differentially expressed miRNAs between ExoRJ and ExoJ. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM3_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM4 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 4. The GO annotation of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoR. A GO annotation of the predicted target genes revealed that 35 target genes were annotated significantly for the 16 miRNAs between ExoRJ and ExoR. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM4_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM4 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 4. The GO annotation of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoR. A GO annotation of the predicted target genes revealed that 35 target genes were annotated significantly for the 16 miRNAs between ExoRJ and ExoR. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM4_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM5 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 5. The KEGG analysis of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoJ. The KEGG analysis of the predicted target genes revealed that 7 regulatory networks were annotated significantly for the 54 differentially expressed miRNAs between ExoRJ and ExoJ. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM5_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM5 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 5. The KEGG analysis of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoJ. The KEGG analysis of the predicted target genes revealed that 7 regulatory networks were annotated significantly for the 54 differentially expressed miRNAs between ExoRJ and ExoJ. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM5_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM6 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 6. The KEGG analysis of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoR. The KEGG analysis of the predicted target genes revealed that 3 regulatory networks were annotated significantly for the 16 differentially expressed miRNAs between ExoRJ and ExoR. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM6_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Title MOESM6 of Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs 
Description Additional file 6. The KEGG analysis of the predicted target genes of the differentially expressed miRNA between ExoRJ and ExoR. The KEGG analysis of the predicted target genes revealed that 3 regulatory networks were annotated significantly for the 16 differentially expressed miRNAs between ExoRJ and ExoR. 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
URL https://springernature.figshare.com/articles/MOESM6_of_Reticuloendotheliosis_virus_and_avian_leukosi...
 
Description Dr. Manman Dai 
Organisation South China Agricultural University
Country China 
Sector Academic/University 
PI Contribution Provided knowledge and expertise on avian disease research
Collaborator Contribution Provided knowledge and expertise on avian disease research
Impact Two joint publications have been generated: 1. Dai M, Zhu S, An Z, You B, Li Z, Yao Y, Nair V, Liao M. Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis. PLoS Pathog. 2023 Oct 11;19(10):e1011685. doi: 10.1371/journal.ppat.1011685. eCollection 2023 Oct. 2. Dai M, Sun H, Zhao L, Wu Q, You B, Xu F, Liao J, Zhu S, Li Z, Yao Y, Nair V, Liao M. Duck CD8 + T Cell Response to H5N1 Highly Pathogenic Avian Influenza Virus Infection In Vivo and In Vitro. J Immunol. 2022 Aug 8;ji2101147. doi: 10.4049/jimmunol.2101147.
Start Year 2022
 
Description Professor Aijian Qin & Kun Qian 
Organisation Yangzhou University
Department Faculty of Veterinary Medicine
Country China 
Sector Academic/University 
PI Contribution Provided knowledge, reagent and information on ALV research
Collaborator Contribution Provided samples and reagent for MDV and ALV research
Impact 15 joint publications have been generated: 1. Qiao D, Wu L, Gu C, Shao H, Yao Y, Qin A, Hu A, Qian K. Establishment and Application of a VP3 Antigenic Domain-based peptide ELISA for the Detection of Antibody against Goose Plague Virus Infection. Front Microbiol. 2023 Nov 23:14:1309807. doi: 10.3389/fmicb.2023.1309807. eCollection 2023. 2. Xu M, QIAN K, Shao H, Yao Y, Nair V, Ye J, and Qin A. 3'UTR of ALV-J can affect viral replication through promoting transcription and mRNA nuclear export. J Virol. 2023 Nov 30;97(11):e0115223. doi: 10.1128/jvi.01152-23. Epub 2023 Oct 30. 3. Cui Z, Weng B, Yao Y, Shao H, Ye J, Qin A, Qian K. Chicken Glycogen Synthase Kinase 3ß Suppresses Innate Immune Responses and Enhances Avian Leukosis Virus Replication in DF-1 Cells. Microbiol Spectr. 2023 May-Jun; 11(3): e05235-22. Published online 2023 Mar 30. doi: 10.1128/spectrum.05235-22 4. Zai X, Shi B, Shao H, Qian K, Ye J, Yao Y, Nair V, Qin A. Recombinant Turkey Herpesvirus expressing H9N2 HA gene from the HVT005/006 site induces better protection than that from the HVT029/031 site. Viruses. 2022, 14(11), 2495; https://doi.org/10.3390/v14112495 5. Zai X, Shi B, Shao H, Qian? K, Ye J, Yao Y, Nair V, Qin A. Identification of a novel insertion site HVT005/006 for the generation of recombinant herpesvirus of turkey (HVT) vector. Front Microbiol. 2022 May 25;13:886873. doi:10.3389/fmicb.2022.886873. 6. Zhao W, Shi J, Yao Y, Shao H, Qin A, Qian K. Isolation, Identification and Genomic Characterization of Chicken Astrovirus Isolates from China. Front. Vet. Sci. 2022 Feb, DOI: 10.3389/fvets.2021.800649 7. Xu M, Qian K, Shao H, Yao Y, Nair V, Ye J, Qin A. Glycosylation of ALV-J envelope protein at sites 17 and 193 is pivotal in the virus replication. J Virol, 2021 Dec 8; JVI0154921. doi: 10.1128/JVI.01549-21. 8. He H, Qiao D, Zhang L, Yao Y, Shao H, Qin A, Qian K. Antiviral Effect of Lithium Chloride on Replication of Marek's Disease Virus in Chicken Embryonic Fibroblasts. Int J Mol Sci. 2021 Nov; 22(22): 12375. doi: 10.3390/ijms222212375 9. Qiao D, He Q, Cheng X, Yao Y, Nair V, Shao H, Qin A and Qian, K. Regulation of avian leukosis virus subgroup J replication by Wnt/ß-catenin signaling pathway. Viruses. 2021 13(10), 1968. DOI: 10.3390/v13101968 10. Xu M, Mu X, Qian K, Shao H, Yao Y, Nair V, Wang J, Ye J, Qin A. Novel mutation of avian leukosis virus subgroup J from Tibetan chickens. Poult Sci. 2021 Mar;100(3):100931. doi: 10.1016/j.psj.2020.12.028. 11. Zhao W, Wu Z, Yao Y, Qian K. The Isolation and Molecular Characterization of an Astrovirus from "Yellow" Chickens, China. Frontiers in Veterinary Science, 27 October 2020 | https://doi.org/10.3389/fvets.2020.581862. 12. Yang F, Feng C, Yao Y, Qin A, Shao H and Qian K. Antiviral effect of baicalin on Marek's disease virus in CEF cells. BMC Veterinary Research. 2020, 16:371. doi: 10.1186/s12917-020-02595-x. 13. Zhou X, Wang L, Shen A, Shen X, Xu M, Qian K, Shao H, Yao Y, Nair V, Ye J, Qin A. Detection of ALV p27 in cloacal swabs and virus isolation medium by sELISA. BMC Vet Res. 2019 Oct 30;15 (1):383. doi: 10.1186/s12917-019-2150-z. 14. Qian K, Tian X, Shao H, Ye J, Yao Y, Nair V, Qin A. Identification of novel B-cell epitope in gp85 of subgroup J avian leukosis virus and its application in diagnosis of disease. BMC Veterinary Research. 2018 Sep 26;14(1):295. doi: 10.1186/s12917-018-1622-x. 15. Qian K, Cheng X, Zhang D, Shao H, Yao Y, Nair V, Qin A. Antiviral effect of lithium chloride on replication of avian leukosis virus subgroup J in cell culture. Arch Virol. 2018 Jan 11. doi: 10.1007/s00705-017-3692-7.
Start Year 2018
 
Description Professor Guozhong Zhuang 
Organisation Henan Agricultural University
Country China 
Sector Academic/University 
PI Contribution Provided knowledge and expertise on MDV research
Collaborator Contribution Provided samples for MDV research
Impact The following joint publications have been generated: 1. Sun A, Yang S, Luo J,Teng M, Xu Y, Wang R, Zhu X, Zheng L, Wu Y, Yao Y, Nair V, Zhang G, Zhuang G. UL28 and UL33 homologs of Marek's disease virus terminase complex involved in the regulation of cleavage and packaging of viral DNA are indispensable for replication in cultured cells. Veterinary Research. 2021, 52:20. 10.1186/s13567-021-00901-5 2. Sun A, Zhao X, Zhu X, Kong Z, Liao Y, Teng M, Yao Y, Luo J, Nair V, Zhuang G, Zhang G. Fully Attenuated meq and pp38 Double Gene Deletion Mutant Virus Confers Superior Immunological Protection against Highly Virulent Marek's Disease Virus Infection. Microbiol Spectr. 2022 Nov 9; doi: 10.1128/spectrum.02871-22 3. Zhuang G, Zhao X, Jin J, Zhu X, Wang R, Zhai Y, Lu W, Liao Y, Teng M, Yao Y, Nair V, Yao W, Sun A, Luo J, Zhang G. Infection phase-dependent dynamics of the viral and host N6-methyladenosine epitranscriptome in the lifecycle of an oncogenic virus in vivo. J Med Virol. 2022 Nov 18. doi: 10.1002/jmv.28324.
Start Year 2019
 
Description Professor Luo 
Organisation Henan Academy of Agricultural Sciences
Country China 
Sector Academic/University 
PI Contribution Provided knowledge, reagent and information on MDV research
Collaborator Contribution Provided samples and reagent for MDV research
Impact 11 joint publications have been generated: 1. Liu JL, Teng M, Zheng LP, Zhu FX, Ma SH, Li LY, Zhang ZH, Chai SJ, Yao Y and Luo J. Emerging Hypervirulent Marek's Disease Virus Variants Significantly Overcome Protection Conferred by Commercial Vaccines. Viruses 2023, 15(7), 1434; doi: 10.3390/v15071434 2. Teng M, Zhu Z, Yao Y, Nair V, Zhang G, Luo J. (2023) Critical Roles of Non-coding RNAs in Avian Oncogenic Marek's Disease Herpesvirus Biology. SCIENCE CHINA Life Sciences 66 2, 251-268; https://doi.org/10.1007/s11427-022-2258-4.Teng M, Liu J, Luo Q, Zheng L, Yao Y, Nair V, Zhang G, Luo J. Efficient Screening and Characterization of Monoclonal Antibodies against MDV-1 Specific Oncoprotein Meq Using the CRISPR/Cas9 Gene Edited Viruses. Viruses, 2023, 15(4), 817; https://doi.org/10.3390/v15040817 3. Zheng L, Teng M, Li G, Zhang W, Wang W, Liu J, Li L, Yao Y, Nair V and Luo J. Current Epidemiology and Co-Infections of Avian Immunosuppressive and Neoplastic Diseases in Chicken Flocks in Central China. Viruses 2022, 14(12), 2599; https://doi.org/10.3390/v14122599 4. Teng M, Zhou Z, Yao Y, Nair V, Zhang G, Luo J. A New Strategy for Efficient Screening and Identification of Monoclonal Antibodies against Oncogenic Avian Herpesvirus Utilizing CRISPR/Cas9-Based Gene-Editing Technology. Viruses. 2022, 14(9), 2045; https://doi.org/10.3390/v14092045 5. Teng M, Yao Y, Nair V, Luo J. Latest Advances of Virology Research Using CRISPR/Cas9-Based Gene-Editing Technology and Its Application to Vaccine Development. Viruses. 2021, 13(5), 779; https://doi.org/10.3390/v13050779 6. Sun A, Yang S, Luo J,Teng M, Xu Y, Wang R, Zhu X, Zheng L, Wu Y, Yao Y, Nair V, Zhang G, Zhuang G. UL28 and UL33 homologs of Marek's disease virus terminase complex involved in the regulation of cleavage and packaging of viral DNA are indispensable for replication in cultured cells. Veterinary Research. 2021, 52:20. 10.1186/s13567-021-00901-5 7. Zhu Z, Teng M, Li H, Zheng L, Liu J, Yao Y, Nair V, Zhang G, Luo J. Virus-encoded miR-155 ortholog in Marek's disease virus promotes cell proliferation via suppressing apoptosis by targeting tumor suppressor WWOX. Veterinary Microbiology. 7 November 2020, https://doi.org/10.1016/j.vetmic.2020.108919 8. Zhu Z, Teng M, Li H, Zheng L, Liu J, Chai S, Yao Y, Nair V, Zhang G, Luo J. Marek's disease virus (Gallid alphaherpesvirus 2, GaHV-2)-encoded miR-M2-5p simultaneously promotes cell proliferation and suppresses apoptosis through RBM24 and MYOD1-mediated signaling pathways. Frontiers in Microbiology. 03 November 2020 | https://doi.org/10.3389/fmicb.2020.596422 9. Luo J, Teng M, Zai X, Tang N, Zhang Y, Mandviwala A, Reddy VRAP, Baigent S, Yao Y, Nair V. Efficient Mutagenesis of Marek's Disease Virus-Encoded microRNAs Using a CRISPR/Cas9-Based Gene Editing System. Viruses. 2020 Apr 20;12(4): E466. doi: 10.3390/v12040466. 10. Zhang Y, Tang N, Luo J, Teng M, Moffat K, Shen Z, Watson M, Nair V#, Yao Y#. Marek's disease virus-encoded miR-155 ortholog critical for the induction of lymphomas is not essential for the proliferation of transformed cell lines. J Virol. 2019 Jun 12. pii: JVI.00713-19. doi: 10.1128/JVI.00713-19. 11. Zhang Y, Luo J, Tang N, Teng M, Reddy VRAP, Moffat K, Shen Z, Nair V#, Yao Y#. Targeted Editing of the pp38 Gene in Marek's Disease Virus-Transformed Cell Lines Using CRISPR/Cas9 System. Viruses. 2019 Apr 26;11(5). pii: E391. doi: 10.3390/v11050391.
Start Year 2018
 
Description Professor Ziqiang Cheng 
Organisation Shandong Agricultural University
Country China 
Sector Academic/University 
PI Contribution Provided knowledge and information on ALV research
Collaborator Contribution Provided samples and reagent for ALV research
Impact 4 publication have been generated: 1. Cui X, Zhang X, Xue J, Yao Y, Zhou D, Cheng Z. TMT-based proteomic analysis reveals integrins involved in the synergistic infection of reticuloendotheliosis virus and avian leukosis virus subgroup J. Journal: BMC Veterinary Research, 18:131, 2022. DOI: 10.1186/s12917-022-03207-6 2. He S, Zheng G, Yang X, Dong J, Zhou D, Nair V, Yao Y, Cheng Z. Avian leukosis virus subgroup J induces B cell anergy mediated by Lyn inhibited BCR signal transduction. Vet Microbiol. 2020 Aug; 247:108781. doi: 10.1016/j.vetmic.2020.108781. 3. Zhu M, Zhou J, Liang Y, Nair V, Yao Y, Cheng Z. CCCH-type zinc finger antiviral protein mediates antiviral immune response by activating T cells. J Leukoc Biol. 2020 Feb;107(2):299-307. doi: 10.1002/JLB.1AB1119-314RRR. Epub 2020 Jan 16. PMID: 31945209. 4. Pang, Y., Zhou, D., Xue, J., Zhou, J., Zhang, Y., Zheng, G., Yuan, S., Yao, Y. and Cheng, Z. Interplay between CTHRC1 and the SU protein of avian leukosis virus subgroup J (ALV-J) facilitates viral replication. Virus Research. 2019. https://doi.org/10.1016/j.virusres.2019.02.014 5. Zhu, M., Zhou, J., Ma, X., Li, G., He, S., Tang, H., Yao, Y. and Cheng, Z. CCCH-type zinc finger antiviral protein is specifically overexpressed in spleen in response to subgroup J avian leukosis virus infection in chicken. Research in Veterinary Science. 2019. 123: 65-70. 6. Zhou J, Zhao GL, Wang XM, Du XS, Su S, Li CG, Nair V, Yao YX, Cheng ZQ. Synergistic Viral Replication of Marek's Disease Virus and Avian Leukosis Virus Subgroup J is Responsible for the Enhanced Pathogenicity in the Superinfection of Chickens. Viruses. 2018 May 18;10(5). pii: E271. doi: 10.3390/v10050271. 7. Zhou D, Xue J, He S, Du X, Zhou J, Li C, Huang L, Nair V, Yao Y, Cheng Z. Reticuloendotheliosis virus and avian leukosis virus subgroup J synergistically increase the accumulation of exosomal miRNAs. Retrovirology. 2018 Jul 3;15(1):45. doi: 10.1186/s12977-018-0427-0.
Start Year 2018
 
Description Yulong Gao 
Organisation Chinese Academy of Agricultural Sciences
Department Harbin Veterinary Research Institute (HVRI)
Country China 
Sector Public 
PI Contribution Provided knowledge, reagent and information on ALV research
Collaborator Contribution Provided samples and reagent for MDV and ALV research
Impact Two publications have been generated: 1. Li K, Liu Y, Xu Z, Zhang Y, Yao Y, Nair V, Liu C, Zhang Y, Gao Y, Qi X, Cui H, Gao L, Wang X. Prevention of Avian Retrovirus Infection in Chickens Using CRISPR-Cas9 Delivered by Marek's Disease Virus. Molecular Therapy - Nucleic Acids 2020 Sep 4; 21:343-353. doi: 10.1016/j.omtn.2020.06.009. 2. Ren C, Xie R, Yao Y, Yu M, Chang F, Xing L, Zhang Y, Liu Y, Wang S, Farooque M, Wang Y, Qi X, Liu C, Zhang Y, Cui H, Li K, Gao L, Pan Q, Nair V, Wang X, Gao Y. MiR-125b Suppression Inhibits Apoptosis and Negatively Regulates Sema4D in Avian Leukosis Virus-Transformed Cells. Viruses. 2019 Aug 7;11(8). pii: E728. doi: 10.3390/v11080728.
Start Year 2018
 
Description AN INTERVIEW WITH PROFESSOR VENUGOPAL NAIR 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Professor Venugopal Nair is a Research Group Leader at The Pirbright Institute, a visiting Professor of Avian Virology at the Department of Zoology, and a Jenner Investigator at the Jenner Institute, University of Oxford. He is also a member of the Microbiology Society, and in this interview, he tells us more about his research into viral diseases of livestock.
Year(s) Of Engagement Activity 2020
URL https://microbiologysociety.org/membership/meet-our-members/focus-area-viruses/an-interview-with-pro...
 
Description Interview by CGTN 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Increased profile of both Institute and The UK-China Centre of Excellence for Research on Avian Diseases (CERAD)
Year(s) Of Engagement Activity 2019
URL https://newseu.cgtn.com/news/2020-01-28/British-and-Chinese-scientists-join-forces-to-fight-avian-di...
 
Description Invited talk on 28th September 2020 on ''Challenges and opportunities for control of infectious animal diseases including zoonosis' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact International Webinar of 'Epistemological approaches to animal disease control programmes with special reference to rabies'
Year(s) Of Engagement Activity 2020
 
Description School visit (Tilingborne) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Stimulating increased interest in science and research
Year(s) Of Engagement Activity 2019
 
Description Science Festival (Cheltenham) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Stimulating increased interest in science and research
Year(s) Of Engagement Activity 2019