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INFLUENZA D VIRUS Technical Paper Cambridge Technologies

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INFLUENZA D VIRUS Technical Paper Cambridge Technologies INFLUENZA D VIRUS Technical Paper Cambridge Technologies Key Points: 1 IDV is a newly identified virus that is in the same family as other influenza viruses. 2 Widespread in the cattle population and commonly found in BRD diagnostic cases. 3 Diagnosis can be made by PCR and virus isolation on nasal swabs. 4 A good candidate for autogenous vaccine, due to a lack of availability of commercial vaccines. Introduction First identified in 2011, Influenza D Development, and Diagnostics at Cam- virus (IDV) has been found in swine, bridge Technologies) was the first to cattle, sheep and goats from multiple isolate this novel virus from an Oklaho- geographic locations worldwide1. A ma hog in 2011. Originally designated member of the Orthomyxoviridae, IDV as C/swine/Oklahoma/1334/2011 (C/ is a single-strand, negative-sense RNA OK), the strain was found to be wide- virus with seven genomic segments. In- spread in cattle throughout the United fluenza C Virus (ICV) is genetically the States6. closest member of the influenza virus AN ONGOING THREAT family, although the two share less than 50% protein sequence identity4. TO CATTLE BRDC is one of the most common, yet most complex, health issues facing today’s cattlemen and veterinarians. Affecting an estimated 97 percent of United States feedlots and 21.2 percent of cattle10, the disease carries an average treatment cost of $23.60 per case15. Often referred to as Shipping Using a combination of diagnostic tests, Fever or Pneumonia, BRDC involves a a research team led by Dr. Ben Hause number of factors such as the age, en- (now the Vice President of Research, vironment, and immunity of the animal as well as numerous bacterial and viral parts of the country for a number of years pathogens. prior. In 2014, Luo, et. al., retrospectively tested sera originally collected from 40 randomly selected Nebraska beef herds in 2003-2004, and found that all 40 contained seropositive adult animals. In addition, approximately 98% of calves born in 2014 had high levels of maternal antibodies against IDV. These results indicated that IDV was present in Nebraska beef cattle Collin, et. al., demonstrated that IDV is since at commonly found in clinical diagnostic least 2003, samples of bovine respiratory disease eight years complex (BRDC), with prevalence simi- prior to the lar to other established BRDC etiological official dis- agents. In addition, they discovered that covery of there are at least two co-circulating lineag- the virus11. es of the strain in U.S. cattle herds, which would indicate that it is endemic in cattle A separate 3 Pictured Above: Positive intense cytoplasmic and that the virus re-assorts frequently . study of staining in trachea respiratory epithelium archived from a calf in T2. One study identified 21 distinct viruses in sera suggested that IDV has been circu- samples taken from a population of feed- lating among cattle in Mississippi since at lot cattle with acute BRDC. Interestingly, least 20045. a statistical analysis of the association between virus detection in asymptomatic DIAGNOSIS and acutely-ill animals found that of those As BRDC often involves a number of 21 viruses, only IDV was a risk factor of bacterial and viral agents, diagnosis can moderate significance (P < 0.15)13. In an- become a multi-step process. Both clinical other study, calves experimentally infected specimens and sera samples can be used in with IDV (via internasal challenge) were an attempt to identify the specific viru- shown to shed virus and seroconvert. The lent strains involved. Nasal swabs can be infected calves transmitted the virus to screened via reverse transcription quanti- IDV-seronegative animals through contact, tative PCR as well as viral isolation, with and they showed mild disease signs (dry further classification conducted with viral coughing, nasal and ocular discharge, de- isolation and sequencing2. pression) as well as tracheal inflammation3. Cambridge Technologies and other select While IDV was first identified in 2011, laboratories have the ability to take the recent studies have indicated that the virus diagnostic process even further, using has been circulating in cattle in different metagenomic sequencing. This process can 2 generate massive amounts of diagnostic technology and inno- veterinarians and their clients sequencing information, utiliz- vative autogenous vaccine formu- a flexible management tool to ing random priming approaches lation, Dr. Hause and Cambridge counter emerging and evolving to non-specifically amplify the Technologies can assist veterinar- diseases, such as the threat nucleic acids present in a sample1. ians and producers in developing of IDV. Metagenomic sequencing brings a targeted, flexible approach CONCLUSION the advantage of not needing against BRDC. proper knowledge of virome Influenza D Virus (IDV) has composition for DNA sequenc- Our industry-leading molecular been shown to be one of numer- ing8, and protocols are available diagnostics, including metag- ous agents in the Bovine Respira- that are capable of detecting both enomics and next-generation tory Disease Complex (BRDC). single-and double-stranded DNA sequencing, identify the specific It is believed to be endemic in U. and RNA viruses9. threats and antigens that need to S. cattle, and is unique among the be included in the product. Then, four known species of A dual approach of real-time the experienced Production team influenza virus. PCR and metagenomics, in care- can formulate and manufacture a fully matched cases and controls, vaccine customized to the needs Cambridge Technologies uti- can provide a rapid means to of each individual customer, lizes cutting-edge diagnostic identify viruses associated com- including antigen concentration, technology to precisely identify plex diseases such as BRDC, multiple adjuvant choices, dose the pathogens contributing to including both close relatives of sizes, and the option of SoliDose BRDC – including IDV. Once the known viruses and “new” highly implants. Should a new strain pathogens have been identified, divergent viruses14. or agent emerge in the future, an autogenous vaccine can be upcoming manufacturing runs of formulated to target those specif- THE CAMBRIDGE the autogenous product can be ADVANTAGE ic bacteria and/or viruses. On- altered to include the new threat. going diagnostic monitoring and Research has shown that an inac- the flexible nature of autogenous tivated IDV vaccine can be pro- Clinical cases of BRD are usually products enable veterinarians and tective against disease caused by treated with antibiotics. However, producers to modify the prod- homologous challenge7. Current- the recent implementation of uct as needed should the disease ly, IDV vaccine is only available in FDA guidance 209 and 213 threats change. autogenous formulation. along with the expansion of the Veterinary Feed Directive has Cambridge Technologies is at the created a need for an forefront of the battle against alternative to man- IDV and BRDC. Our Research aging animal health. and Diagnostic teams are led by Autogenous vaccines Dr. Ben Hause, who first identi- from Cambridge fied IDV. Using industry-leading Technologies offer 3 SOURCES 1. Allander, T, Tammi MT, Eriksson M, Bjerkner A, 9. Hause, BM, Collin EA, Anderson J, Hesse RA, Tiveljung-Lindell A, Andersson B. Cloning of a hu- Anderson G. Bovine rhinitis viruses are common in man parvovirus by molecular screening of respiratory U.S. cattle with bovine respiratory disease. PLaS ONE. tract samples. Proc. Natl Acad Sci. 2005; 102:12891- 2015; 10:e0121998. 12896. 10. Johnson K, Pendell D. Economic Impact of 2. Chipponi C, Faccini S, De Mattia A, Baioni L, Reducing Bovine Respiratory Disease in United States Barbieri I, Rosignoli C, Nigrelli A, Foni E. Detection Beef Cattle Feedlots. https://ageconsearch.umn.edu/ of Influenza D Virus among Swine and Cattle, Italy. record/206872/files/BRD%20poster%20AAEA%20 Emerging Infectious Diseases. 2016; 22(2):352-354. final%20to%20upload%20with%20cover%20page. pdf. Presented July, 2015. Accessed July 22, 2017. 3. Collin EA, Sheng Z, Lang Y, Ma W, Hause BM, Li, F. Cocirculation of Two Distinct Genetic and Anti- 11. Luo J, Ferguson L, Smith DR, Woolums AR, genetic Lineages of Proposed Influenza D Virus in Epperson WB, Wan XF. Serological evidence for high Cattle. Journal of Virology. 2015; 89(2):1036-1042. prevalence of Influenza D Viruses in Cattle, Nebras- ka, United States, 2003-2004. Virology. 2017; 501:88- 4. Ferguson, L, Olivier AK, Genova S, Epperson WB, 91. Smith DR, Schneider L, Barton K, McCuan K, Webby RJ, Wan, XF. Pathogenesis of Influenza D Virus in 12. Meat & Livestock Australia. Bovine Respiratory Cattle. Journal of Virology. 2016; 90(12): 5636-5642. Disease. https://www.mla.com.au/research-and-de- velopment/animal-health-welfare-and-biosecurity/dis- 5. Ferguson L, Eckard L, Epperson WB, Long LP, eases/infectious/bovine-respiratory-disease/. Updat- Smith D, Huston C, Genova S, Webby R, Wan XF. ed 2016. Accessed July 23, 2017. Influenza D virus infection in Mississippi beef cattle. Virology. 2015; 486:28-34. 13. Mitra, N, Cernicchiaro N, Torres S, Li F, Hause BM. Metagenomic characterization of the virome 6. Hause BM, Collin EA, Liu R, Huang B, Sheng Z, association with bovine respiratory disease in feedlot Lu W, Wang D, Nelson EA, Li F. Characterization of cattle identified novel viruses and suggests an etiologic a Novel Influenza Virus in Cattle and Swine: Proposal role for influenza D virus. Journal of General Virolo- for a New Genus in the Orthomyxoviridae Family. gy. 2016 Aug; 97(8):1771-1784. mBio 5(2):e00031-14. 14. Ng TFF, Kondov NO, Deng X, Van Eenennaam 7. Hause BM, Huntimer L, Falkenberg S, Henningson A, Neibergs H, Delwart E. A Metagenomics and J, Lechtenberg K, Halbur T. An inactivated influenza Case-Control Study to Identify Viruses Associated D virus vaccine partially protects cattle from respira- with Bovine Respiratory Diseases. Journal of Virolo- tory disease caused by homologous challenge.
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