A novel antigen capture ELISA for the specific detection of IgG antibodies to elephant endotheliotropic herpes virus

BMC Veterinary Research

Byron Martina^1,11  Akbar Dastjerdi²  Paul D. Ling^1,10  Albert D. M. E. Osterhaus^1,11  Nic Masters⁸  Sarah Chapman¹  Lauren Howard⁹  Erin Latimer⁴  Willem Schaftenaar³  Sarah E. van Rossum-Fikkert⁵  Víctor Rodríguez Prieto⁶  Petra B. van den Doel⁷ 

[1] East-Midland Zoological Society, Twycross Zoo, Warwickshire, UK;Animal and Plant Health Agency, Addlestone, UK;Veterinary services, Rotterdam Zoo, Rotterdam, The Netherlands;Smithsonian Conservation Biology Institute, Smithsonian’s National Zoo, Washington, DC, USA;Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands;VISAVET Centre, Animal Health Department, Complutense University of Madrid, Madrid, Spain;ViroScience Lab, Erasmus Medical Center, Erasmus MC, Room Ee1714, dr. Molewaterplein 50, Rotterdam, 3015, GE, The Netherlands;Veterinary Services, Zoological Society of London, London, UK;Department of Animal Health, Houston Zoo, Inc., Houston, TX, USA;Department of Molecular Virology and Microbiology, Baylor’s College of Medicine, Houston, TX, USA;Artemis One Health Research Institute, Utrecht, The Netherlands

关键词: Seroprevalence;    ELISA;    Glycoprotein B;    Asian elephant;    EEHV;   

Others  :  1224349
DOI  :  10.1186/s12917-015-0522-6

 received in 2015-02-04, accepted in 2015-07-31,  发布年份 2015

【 摘 要 】

Background

Elephants are classified as critically endangered animals by the International Union for Conservation of Species (IUCN). Elephant endotheliotropic herpesvirus (EEHV) poses a large threat to breeding programs of captive Asian elephants by causing fatal haemorrhagic disease. EEHV infection is detected by PCR in samples from both clinically ill and asymptomatic elephants with an active infection, whereas latent carriers can be distinguished exclusively via serological assays. To date, identification of latent carriers has been challenging, since there are no serological assays capable of detecting seropositive elephants.

Results

Here we describe a novel ELISA that specifically detects EEHV antibodies circulating in Asian elephant plasma/serum. Approximately 80 % of PCR positive elephants display EEHV-specific antibodies. Monitoring three Asian elephant herds from European zoos revealed that the serostatus of elephants within a herd varied from non-detectable to high titers. The antibody titers showed typical herpes-like rise-and-fall patterns in time which occur in all seropositive animals in the herd more or less simultaneously.

Conclusions

This study shows that the developed ELISA is suitable to detect antibodies specific to EEHV. It allows study of EEHV seroprevalence in Asian elephants. Results confirm that EEHV prevalence among Asian elephants (whether captive-born or wild-caught) is high.

【 授权许可】

   
2015 van den Doel et al.

【 图 表 】

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【 参考文献 】

• [1]Davis-Poynter NJ, Farrell HE. Masters of deception: a review of herpesvirus immune evasion strategies. Immunol Cell Biol. 1996; 74:513-522.
• [2]Greenwood AD, Tsangaras K, Ho SY, Szentiks CA, Nikolin VM, Ma G, Damiani A, East ML, Lawrenz A, Hofer H, Osterrieder N. A potentially fatal mix of herpes in zoos. Curr Biol. 2012; 22:1727-1731.
• [3]Cantey JB, Sanchez PJ. Neonatal herpes simplex virus infections: past progress and future challenges. Pediatr Infect Dis J. 2013; 32:1205-1207.
• [4]Pruitt AA. Nervous system viral infections in immunocompromised hosts. Handb Clin Neurol. 2014; 123:685-704.
• [5]McCully RM, Basson PA, Pienaar JG, Erasmus BJ, Young E. Herpes nodules in the lung of the African elephant (Loxodonta africana (Blumebach, 1792)). Onderstepoort J Vet Res. 1971; 38:225-235.
• [6]Jacobson ER, Sundberg JP, Gaskin JM, Kollias GV, O’Banion MK. Cutaneous papillomas associated with a herpesvirus-like infection in a herd of captive African elephants. J Am Vet Med Assoc. 1986; 189:1075-1078.
• [7]Ossent P, Guscetti F, Metzler AE, Lang EM, Rubel A, Hauser B. Acute and fatal herpesvirus infection in a young Asian elephant (Elephas maximus). Vet Pathol. 1990; 27:131-133.
• [8]Metzler AE, Ossent P, Guscetti F, Rubel A, Lang EM. Serological evidence of herpesvirus infection in captive Asian elephants (Elephas maximus). J Wildl Dis. 1990; 26:41-49.
• [9]Bhat MN, Manickam R, Kumanan K. Serological evidence of bovine herpesviruses 1 and 2 in Asian elephants. J Wildl Dis. 1997; 33:919-920.
• [10]Richman LK, Montali RJ, Garber RL, Kennedy MA, Lehnhardt J, Hildebrandt T, Schmitt D, Hardy D, Alcendor DJ, Hayward GS. Novel endotheliotropic herpesviruses fatal for Asian and African elephants. Science. 1999; 283:1171-1176.
• [11]Davison AJ, Eberle R, Ehlers B, Hayward GS, McGeoch DJ, Minson AC, Pellett PE, Roizman B, Studdert MJ, Thiry E. The order Herpesvirales. Arch Virol. 2009; 154:171-177.
• [12]Richman LK, Zong JC, Latimer EM, Lock J, Fleischer R, Heaggans SY, et al. Elephant Endotheliotropic Herpesviruses EEHV1A, EEHV1B and EEHV2 from Cases of Hemorrhagic Disease are Highly Diverged from Other Mammalian Herpesviruses and May Form a New Subfamily. J Virol. 2014.
• [13]Ling PD, Reid JG, Qin X, Muzny DM, Gibbs R, Petrosino J, Peng R, Zong JC, Heaggans SY, Hayward GS. Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 1A. Genome Announc. 2013; 1: Article ID e0010613
• [14]Wilkie GS, Davison AJ, Watson M, Kerr K, Sanderson S, Bouts T, Steinbach F, Dastjerdi A. Complete genome sequences of elephant endotheliotropic herpesviruses 1A and 1B determined directly from fatal cases. J Virol. 2013; 87:6700-6712.
• [15]Atkins L, Zong JC, Tan J, Mejia A, Heaggans SY, Nofs SA, Stanton JJ, Flanagan JP, Howard L, Latimer E et al.. Elephant endotheliotropic herpesvirus 5, a newly recognized elephant herpesvirus associated with clinical and subclinical infections in captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2013; 44:136-143.
• [16]Latimer E, Zong JC, Heaggans SY, Richman LK, Hayward GS. Detection and evaluation of novel herpesviruses in routine and pathological samples from Asian and African elephants: identification of two new probosciviruses (EEHV5 and EEHV6) and two new gammaherpesviruses (EGHV3B and EGHV5). Vet Microbiol. 2011; 147:28-41.
• [17]Schaftenaar W, Reid C, Martina B, Fickel J, Osterhaus AD. Nonfatal clinical presentation of elephant endotheliotropic herpes virus discovered in a group of captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2010; 41:626-632.
• [18]Stanton JJ, Nofs SA, Zachariah A, Kalaivannan N, Ling PD. Detection of elephant endotheliotropic herpesvirus infection among healthy Asian elephants (Elephas maximus) in South India. J Wildl Dis. 2014; 50:279-287.
• [19]Stanton JJ, Zong JC, Eng C, Howard L, Flanagan J, Stevens M, Schmitt D, Wiedner E, Graham D, Junge RE et al.. Kinetics of viral loads and genotypic analysis of elephant endotheliotropic herpesvirus-1 infection in captive Asian elephants (Elephas maximus). J Zoo Wildl Med. 2013; 44:42-54.
• [20]Cairns TM, Fontana J, Huang ZY, Whitbeck JC, Atanasiu D, Rao S, Shelly SS, Lou H, Ponce de Leon M, Steven AC et al.. Mechanism of neutralization of herpes simplex virus by antibodies directed at the fusion domain of glycoprotein B. J Virol. 2014; 88:2677-2689.
• [21]Spindler N, Diestel U, Stump JD, Wiegers AK, Winkler TH, Sticht H, Mach M, Muller YA. Structural basis for the recognition of human cytomegalovirus glycoprotein B by a neutralizing human antibody. PLoS Pathog. 2014; 10: Article ID e1004377
• [22]Fickel J, Lieckfeldt D, Richman LK, Streich WJ, Hildebrandt TB, Pitra C. Comparison of glycoprotein B (gB) variants of the elephant endotheliotropic herpesvirus (EEHV) isolated from Asian elephants (Elephas maximus). Vet Microbiol. 2003; 91:11-21.
• [23]Zong JC, Latimer EM, Long SY, Richman LK, Heaggans SY, Hayward GS. Comparative Genome Analysis of Four Elephant Endotheliotropic Herpesviruses EEHV3, EEHV4, EEHV5 and EEHV6 from Cases of Hemorrhagic Disease or Viremia. J Virol. 2014.
• [24]Stanton JJ, Zong JC, Latimer E, Tan J, Herron A, Hayward GS, Ling PD. Detection of pathogenic elephant endotheliotropic herpesvirus in routine trunk washes from healthy adult Asian elephants (Elephas maximus) by use of a real-time quantitative polymerase chain reaction assay. Am J Vet Res. 2010; 71:925-933.
• [25]Sprengart ML, Porter AG. Functional importance of RNA interactions in selection of translation initiation codons. Mol Microbiol. 1997; 24:19-28.
• [26]Liao PY, Gupta P, Petrov AN, Dinman JD, Lee KH. A new kinetic model reveals the synergistic effect of E-, P- and A-sites on +1 ribosomal frameshifting. Nucleic Acids Res. 2008; 36:2619-2629.
• [27]Lindsley D, Gallant J. On the directional specificity of ribosome frameshifting at a “hungry” codon. Proc Natl Acad Sci U S A. 1993; 90:5469-5473.
• [28]Gallant J, Bonthuis P, Lindsley D. Evidence that the bypassing ribosome travels through the coding gap. Proc Natl Acad Sci U S A. 2003; 100:13430-13435.
• [29]Hardman K, Dastjerdi A, Gurrala R, Routh A, Banks M, Steinbach F, Bouts T. Detection of elephant endotheliotropic herpesvirus type 1 in asymptomatic elephants using TaqMan real-time PCR. Vet Rec. 2012; 170:205.