Turkeys.

2020-21 Rapid Ag: Re-emerging Turkey Arthritis Reovirus in Minnesota Turkeys: Comparative Pathogenesis and Development of Control Strategies (renewal)

May 1, 2019

Principal Leader

Sunil Kumar Mor and Rob Porter

Department

Veterinary Population Medicine

The Problem

Cases of turkey lameness caused by turkey arthritis reovirus (TARV) continue to increase even with the use of autogenous vaccines probably because of virus variation. Newer vaccines are needed that can protect against virus variants, and are cost effective and easy to administer. Using RARF (and industry) funds, we have sequenced 96 TARV and 20 TERV strains and have detected strains with deletions in sigma C protein. All TARV sequences were divided into three main groups based on genetic and antigenic characterization. In 2017-18, we detected TARVs in less than 6-week-old turkeys as well as in round heart syndrome. We have also successfully generated subunit vaccine in vitro. The objectives of this project are to study the comparative pathogenesis of TARVs and TERVs and in vivo evaluation of subunit vaccines.

Background

We at MVDL have seen increased submissions of lame turkeys with TARV-induced tenosynovitis. Lately, other changes have been seen in the clinical picture of some cases e.g., cartilage erosions, which have not been previously described, and appearance of clinical lameness in younger turkeys (age 6-8 weeks). In some instances, lameness affects 35-70% of a flock resulting in huge economic losses. A turkey company in Pennsylvania lost an estimated $3 million in 2014 due to re-emerging TARV-associated lameness.1 Custom autogenous vaccines made with 2011 strains helped slow down the infection initially but now is ineffective against the newly evolved strains. This failure appears to be due to virus variation; viruses isolated in 2014 were antigenically different from 2011 isolates based on virus neutralization assays.2 Zhong et al.16 reported continued evolution of virulence in chicken reoviruses based on the genetic and pathogenic characterization of 11 avian reovirus isolates from northern China. Another burning question is the difference between reoviruses that cause lameness vs those that cause enteritis thereby prompting us to include a small comparative pathogenesis study. 

Anticipated benefits: Analyzing the complete genome of TARVs from Minnesota and neighboring states has helped us in characterizing newly emerging TARVs, their relationship with 2011 isolates and those used in autogenous vaccines, virus movement, and reassortment events. We have developed diagnostic tests (real-time RT-PCR and whole virus ELISA) to specifically detect TARVs and its antibodies. We have enough whole genome sequence data (achieved with funds from RARF and industry) that will help us find molecular markers for differentiation of TERVs from TARVs in the remaining period of the current grant. These data will help in the development of diagnostic tools for early detection of TARVs leading to the implementation of preventive and control measures. Also, the empirical approach of strain selection for vaccine development will be replaced with scientifically-based criteria by studying the types of strains (and the relationships among them, if any) circulating in the population. The pathogenesis study will also help in proper planning of prevention and control measures.

Pichinde virus-based vaccine vector: Dr. Ly has recently developed a novel Pichinde virus (PICV)- based vaccine vector (rP18tri) that packages three viral genomic RNA segments and encodes as many as two foreign genes. By using the influenza virus HA and NP genes as model antigens, his team found that this vector induced strong humoral and cellular immunity when given by intraperitoneal, intramuscular, intranasal, or oral routes and protected mice against a lethal dose of influenza virus.4 Interestingly, administration of a booster dose further enhanced the immune response, a feature that distinguishes this from other known live viral vectors. The rP18tri does not appear to induce strong anti-vector immunity because the PICV glycoprotein is highly glycosylated, which acts as a glycan shield against neutralizing antibodies.5 Also, there is virtually no pre-existing immunity against PICV in birds, since the natural hosts for PICV are rice rats found only in Colombia, South America. The PICV appears to have a wide host tropism, as it can infect cells from different animals including chickens (Fig. 2), and can induce neutralizing antibodies as was observed in modeled influenza virus HA antigen in vaccinated chickens (Fig. 3). This vector also appears to be safe, as vaccinated chickens do not transmit the virus to unvaccinated cage-mates (data not shown). Because of these unique features, PICV can be an excellent vector for TARV vaccines.

Objectives and Goals

  1. To study the comparative pathogenesis of TARV and TERV
  2. In vivo evolution of subunit TARV vaccines

References

  1. Lu, H. et al. 2015. Sci. Rep. 5:14727.
  2. Markis, M. et al. 2015. AARP Convention, Boston, MA.
  3. Goldenberg, D. et al. 2016. Vaccine. 34:3178-3183.
  4. Dhanwani, R. et al. 2016. J. Virol. 90:2551–2560.
  5. Sommerstein, R. et al. 2015. PLoS Pathol. 11:e1005276.
  6. Martin, D. P. et al. 2015. Virus Evolution, 1: vev003.
  7. Ball, L., 2005. Virus Taxonomy: Classification and Nomenclature of Viruses: 8th Rpt of International Committee on Taxonomy of Viruses, Elsevier, Amsterdam, pp. 3–8.
  8. Goldenberg, D. et al. 2011. J. Virol. Methods. 177:80-86.
  9. Mor et al. 2015. J Virol Methods. Sep 1; 221:131-4. doi: 10.1016/j.jviromet.2015.04.025.
  10. Chiang et al. 2000. J Vet Diagn Invest. 12:381-384.
  11. Wickramasinghe, R. et al. 1993. Virology. 194, 688-696.
  12. Wan, J. 2012. Vet. Immunol. Immunopathol., 147:154-160.
  13. Sharafeldin, T.A. et al. 2015. Vet. Res. 46:11-18.
  14. Mor S.K. et al. 2014. Avian Dis. 58:404-407.
  15. Sharafeldin, T.A. et al. 2014. Avian Pathol. 43:371-378.
  16. Zhong, L. et al. 2016. Sci Rpts 6:35271 | DOI: 10.1038/srep35271