A Point Mutation in a Herpesvirus Co-Determines Neuropathogenicity and Viral Shedding.
Abstract: A point mutation in the DNA polymerase gene in equine herpesvirus type 1 (EHV-1) is one determinant for the development of neurological disease in horses. Three recently conducted infection experiments using domestic horses and ponies failed to detect statistically significant differences in viral shedding between the neuropathogenic and non-neuropathogenic variants. These results were interpreted as suggesting the absence of a consistent selective advantage of the neuropathogenic variant and therefore appeared to be inconsistent with a systematic increase in the prevalence of neuropathogenic strains. To overcome potential problems of low statistical power related to small group sizes in these infection experiments, we integrated raw data from all three experiments into a single statistical analysis. The results of this combined analysis showed that infection with the neuropathogenic EHV-1 variant led to a statistically significant increase in viral shedding. This finding is consistent with the idea that neuropathogenic strains could have a selective advantage and are therefore systematically increasing in prevalence in domestic horse populations. However, further studies are required to determine whether a selective advantage indeed exists for neuropathogenic strains.
Publication Date: 2017-01-10 PubMed ID: 28075374PubMed Central: PMC5294975DOI: 10.3390/v9010006Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research discusses how a specific mutation in the equine herpesvirus type 1 (EHV-1) gene can cause neurological disease in horses, affecting viral shedding rates. It investigates whether the neuropathogenic variant has a selective advantage over non-neuropathogenic variants.
Objective and Methods of the Study
- The purpose of this research was to understand how a point mutation in the DNA polymerase gene in equine herpesvirus type 1 (EHV-1) contributes towards neuropathogenicity and changes in viral shedding.
- The researchers performed several infection experiments using domestic horses and ponies to compare viral shedding between neuropathogenic (disease-causing) and non-neuropathogenic variants of EHV-1.
Initial Results and Assumptions
- Contrary to what might be expected, initial experiments did not show a significant difference in viral shedding between both variants.
- This result was interpreted as having no evidence for a consistent selective advantage of the neuropathogenic variant, contrary to theories suggesting an increase of neuropathogenic strains in the domestic horse population.
Refinement of the Analysis Method
- In efforts to evade the issue of low statistical power due to small group sizes in individual experiments, the researchers combined raw data from all experiments for a single statistical analysis.
- This integrated analysis method improved the statistical strength of the results compared to the individual experiments.
New Findings and Future Directions
- The revised analysis showed that horses infected with the neuropathogenic variant exhibited a statistically significant increase in viral shedding compared to the non-neuropathogenic variant.
- These findings suggest that neuropathogenic strains might indeed have a selective advantage, consistent with increases in prevalence observed in domestic horse populations.
- However, to validate these results, the researchers recommend additional studies to better determine if such selective advantage exists.
Cite This Article
APA
Franz M, Goodman LB, Van de Walle GR, Osterrieder N, Greenwood AD.
(2017).
A Point Mutation in a Herpesvirus Co-Determines Neuropathogenicity and Viral Shedding.
Viruses, 9(1), 6.
https://doi.org/10.3390/v9010006 Publication
Researcher Affiliations
- Department of Wildlife Diseases, Leibniz Institute for Zoo and Wildlife Research, Berlin 10315, Germany. m.franz@izw-berlin.de.
- Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14850, USA. laura.goodman@cornell.edu.
- Baker Institute for Animal Health, Cornell University, Ithaca, NY 14850, USA. grv23@cornell.edu.
- Institut für Virologie, Freie Universität Berlin, Robert Von Ostertag-Str. 7 - 13, Berlin 14163, Germany. no.34@fu-berlin.de.
- Department of Wildlife Diseases, Leibniz Institute for Zoo and Wildlife Research, Berlin 10315, Germany. greenwood@izw-berlin.de.
- Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, Berlin 14163, Germany. greenwood@izw-berlin.de.
MeSH Terms
- Animals
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / pathogenicity
- Horses
- Point Mutation
- Virulence
- Virus Shedding
Conflict of Interest Statement
The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.
References
This article includes 34 references
- Lunn DP, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K, Pusterla N, Townsend HG. Equine herpesvirus-1 consensus statement.. J Vet Intern Med 2009 May-Jun;23(3):450-61.
- Perkins GA, Goodman LB, Tsujimura K, Van de Walle GR, Kim SG, Dubovi EJ, Osterrieder N. Investigation of the prevalence of neurologic equine herpes virus type 1 (EHV-1) in a 23-year retrospective analysis (1984-2007).. Vet Microbiol 2009 Nov 18;139(3-4):375-8.
- Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N. Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.. J Virol 2006 Apr;80(8):4047-60.
- Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL, Mercorelli B, Kydd JH, Palù G, Smith KC, Osterrieder N, Davis-Poynter N. A point mutation in a herpesvirus polymerase determines neuropathogenicity.. PLoS Pathog 2007 Nov;3(11):e160.
- Van de Walle GR, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N. A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease.. J Infect Dis 2009 Jul 1;200(1):20-5.
- US Department of Agriculture Animal and Plant Health Inspection Service. Equine Herpesvirus Myeloencephalopathy: A Potentially Emerging Disease. .
- Allen GP, Bolin DC, Bryant U, Carter CN, Giles RC, Harrison LR, Hong CB, Jackson CB, Poonacha K, Wharton R, Williams NM. Prevalence of latent, neuropathogenic equine herpesvirus-1 in the Thoroughbred broodmare population of central Kentucky.. Equine Vet J 2008 Mar;40(2):105-10.
- Smith KL, Allen GP, Branscum AJ, Frank Cook R, Vickers ML, Timoney PJ, Balasuriya UB. The increased prevalence of neuropathogenic strains of EHV-1 in equine abortions.. Vet Microbiol 2010 Feb 24;141(1-2):5-11.
- Henninger RW, Reed SM, Saville WJ, Allen GP, Hass GF, Kohn CW, Sofaly C. Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center.. J Vet Intern Med 2007 Jan-Feb;21(1):157-65.
- McGill R, Tukey JW, Larsen WA. Variations of box plots. Am. Stat. 1978;32:12–16.
- Fournier DA, Skaug HJ, Ancheta J, Ianelli J, Magnusson A, Maunder MN, Nielsen A, Sibert J. AD Model Builder: Using automatic differentiation for statistical inference of highly parameterized complex nonlinear models. Optim. Methods Softw. 2012;27:233–249.
- R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: 2015.
- Dryad Digital Repository. [(accessed on 5 January 2017)]. Available online: http://dx.doi.org/10.5061/dryad.61k7n.
- Alizon S, de Roode JC, Michalakis Y. Multiple infections and the evolution of virulence.. Ecol Lett 2013 Apr;16(4):556-67.
- Mideo N, Alizon S, Day T. Linking within- and between-host dynamics in the evolutionary epidemiology of infectious diseases.. Trends Ecol Evol 2008 Sep;23(9):511-7.
- Alizon S, van Baalen M. Multiple infections, immune dynamics, and the evolution of virulence.. Am Nat 2008 Oct;172(4):E150-68.
- Brown SP, Grenfell BT. An unlikely partnership: parasites, concomitant immunity and host defence.. Proc Biol Sci 2001 Dec 22;268(1485):2543-9.
- Allen GP, Breathnach CC. Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viraemia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV-1.. Equine Vet J 2006 May;38(3):252-7.
- Pusterla N, Hussey GS. Equine herpesvirus 1 myeloencephalopathy.. Vet Clin North Am Equine Pract 2014 Dec;30(3):489-506.
- Soboll Hussey G, Ashton LV, Quintana AM, Lunn DP, Goehring LS, Annis K, Landolt G. Innate immune responses of airway epithelial cells to infection with equine herpesvirus-1.. Vet Microbiol 2014 May 14;170(1-2):28-38.
- Goehring LS, Hussey GS, Ashton LV, Schenkel AR, Lunn DP. Infection of central nervous system endothelial cells by cell-associated EHV-1.. Vet Microbiol 2011 Mar 24;148(2-4):389-95.
- Vandekerckhove AP, Glorieux S, Gryspeerdt AC, Steukers L, Duchateau L, Osterrieder N, Van de Walle GR, Nauwynck HJ. Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants.. J Gen Virol 2010 Aug;91(Pt 8):2019-2028.
- Negussie H, Li Y, Tessema TS, Nauwynck HJ. Replication characteristics of equine herpesvirus 1 and equine herpesvirus 3: comparative analysis using ex vivo tissue cultures.. Vet Res 2016 Jan 15;47:19.
- Alizon S, Hurford A, Mideo N, Van Baalen M. Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future.. J Evol Biol 2009 Feb;22(2):245-59.
- Bull JJ, Lauring AS. Theory and empiricism in virulence evolution.. PLoS Pathog 2014 Oct;10(10):e1004387.
- Cressler CE, McLEOD DV, Rozins C, VAN DEN Hoogen J, Day T. The adaptive evolution of virulence: a review of theoretical predictions and empirical tests.. Parasitology 2016 Jun;143(7):915-930.
- Paul RE, Lafond T, Müller-Graf CD, Nithiuthai S, Brey PT, Koella JC. Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections.. BMC Evol Biol 2004 Sep 8;4:30.
- Salvaudon L, Héraudet V, Shykoff JA. Parasite-host fitness trade-offs change with parasite identity: genotype-specific interactions in a plant-pathogen system.. Evolution 2005 Dec;59(12):2518-24.
- Mackinnon MJ, Gandon S, Read AF. Virulence evolution in response to vaccination: the case of malaria.. Vaccine 2008 Jul 18;26 Suppl 3(48-5):C42-52.
- Mackinnon MJ, Read AF. GENETIC RELATIONSHIPS BETWEEN PARASITE VIRULENCE AND TRANSMISSION IN THE RODENT MALARIA PLASMODIUM CHABAUDI.. Evolution 1999 Jun;53(3):689-703.
- Ferguson HM, Mackinnon MJ, Chan BH, Read AF. Mosquito mortality and the evolution of malaria virulence.. Evolution 2003 Dec;57(12):2792-804.
- Atkins KE, Read AF, Savill NJ, Renz KG, Walkden-Brown SW, Woolhouse ME. Modelling Marek's disease virus (MDV) infection: parameter estimates for mortality rate and infectiousness.. BMC Vet Res 2011 Nov 11;7:70.
- Alizon S, Michalakis Y. Adaptive virulence evolution: the good old fitness-based approach.. Trends Ecol Evol 2015 May;30(5):248-54.
- Schmid Hempel P, Schmid-Hempel P. Evolutionary Parasitologythe Integrated Study of Infections, Immunology, Ecology, and Genetics. Oxford, UK: 2011.
Citations
This article has been cited 3 times.- Sutton G, Garvey M, Cullinane A, Jourdan M, Fortier C, Moreau P, Foursin M, Gryspeerdt A, Maisonnier V, Marcillaud-Pitel C, Legrand L, Paillot R, Pronost S. Molecular Surveillance of EHV-1 Strains Circulating in France during and after the Major 2009 Outbreak in Normandy Involving Respiratory Infection, Neurological Disorder, and Abortion.. Viruses 2019 Oct 4;11(10).
- Garvey M, Lyons R, Hector RD, Walsh C, Arkins S, Cullinane A. Molecular Characterisation of Equine Herpesvirus 1 Isolates from Cases of Abortion, Respiratory and Neurological Disease in Ireland between 1990 and 2017.. Pathogens 2019 Jan 15;8(1).
- Matczuk AK, Skarbek M, Jackulak NA, Bażanów BA. Molecular characterisation of equid alphaherpesvirus 1 strains isolated from aborted fetuses in Poland.. Virol J 2018 Dec 3;15(1):186.
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