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PloS one2013; 8(10); e77754; doi: 10.1371/journal.pone.0077754

Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

Abstract: Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.
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Publication Date: 2013-10-11 PubMed ID: 24147074PubMed Central: PMC3795644DOI: 10.1371/journal.pone.0077754Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study shows that equine herpesvirus 5 (EHV 5), a type of gammaherpesvirus, can induce lung fibrosis, a lung disease, in horses when directly inoculated into their lungs. This provides the first concrete evidence that gammaherpesviruses can cause lung fibrosis in their natural host.

Objective of the Research

  • The main aim of this research was to experimentally demonstrate whether the equine gammaherpesvirus (γHV), known as equine herpesvirus 5 (EHV 5), can cause lung fibrosis or equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease, in its natural host, the horse.

Research Methodology

  • The researchers inoculated EHV 5 isolated from horses already affected with EMPF into the lungs of clinically healthy horses.
  • Before and after the inoculation, they measured neutralizing antibody titers in the horses in order to monitor immune system responses.
  • PCR and virus isolation techniques were used to detect EHV 5 in blood samples taken during the horse’s life, as well as in lung tissue samples collected after euthanasia.

Research Findings

  • The experiment demonstrated that nodular pulmonary fibrosis and induction of myofibroblasts occurred in horses after inoculating them with EHV 5.
  • The mean lung collagen level in the inoculated horses significantly increased compared to the control horses, indicating the presence of fibrosis.
  • The percentage of interstitial collagen also significantly increased in the inoculated horses, providing further evidence of induced fibrosis.
  • It was difficult to detect the virus in the horses during the experiment, but EHV 5 antigen was identified in lung tissue through immunohistochemistry, hence demonstrating its presence.

Conclusion of the Research

  • The study concluded that EHV 5 can induce lung fibrosis in horses, suggesting that fibrosis may occur while the virus is dormant within the lung.
  • This research provides the first documented case of a gammaherpesvirus inducing lung fibrosis in its natural host, an important step in understanding the pathogenesis of pulmonary fibrosis.

Cite This Article

APA
Williams KJ, Robinson NE, Lim A, Brandenberger C, Maes R, Behan A, Bolin SR. (2013). Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5. PLoS One, 8(10), e77754. https://doi.org/10.1371/journal.pone.0077754

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 10
Pages: e77754
PII: e77754

Researcher Affiliations

Williams, Kurt J
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America.
Robinson, N Edward
    Lim, Ailam
      Brandenberger, Christina
        Maes, Roger
          Behan, Ashley
            Bolin, Steven R

              MeSH Terms

              • Animals
              • Antibodies, Viral / immunology
              • Gammaherpesvirinae / immunology
              • Gammaherpesvirinae / pathogenicity
              • Horse Diseases / immunology
              • Horse Diseases / metabolism
              • Horse Diseases / virology
              • Horses
              • Pulmonary Fibrosis / immunology
              • Pulmonary Fibrosis / metabolism
              • Pulmonary Fibrosis / virology

              Conflict of Interest Statement

              This study was funded by Pfizer Animal Health, New York, N.Y. There are no other declarations to be made related to employment, consultancy, patents, products in development etc. related to this manuscript. The authors' relationship with Pfizer Animal Health does not alter their adherence to all PLOS ONE policies on sharing data and materials.

              References

              This article includes 59 references
              1. Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature.. Eur Respir Rev 2012 Dec 1;21(126):355-61.
                doi: 10.1183/09059180.00002512pmc: PMC9487229pubmed: 23204124google scholar: lookup
              2. Crystal RG, Bitterman PB, Mossman B, Schwarz MI, Sheppard D, Almasy L, Chapman HA, Friedman SL, King TE Jr, Leinwand LA, Liotta L, Martin GR, Schwartz DA, Schultz GS, Wagner CR, Musson RA. Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working group.. Am J Respir Crit Care Med 2002 Jul 15;166(2):236-46.
                doi: 10.1164/rccm.2201069pubmed: 12119236google scholar: lookup
              3. Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis.. Am J Physiol Lung Cell Mol Physiol 2008 Feb;294(2):L152-60.
                pubmed: 17993587doi: 10.1152/ajplung.00313.2007google scholar: lookup
              4. Tang YW, Johnson JE, Browning PJ, Cruz-Gervis RA, Davis A, Graham BS, Brigham KL, Oates JA Jr, Loyd JE, Stecenko AA. Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis.. J Clin Microbiol 2003 Jun;41(6):2633-40.
                doi: 10.1128/JCM.41.6.2633-2640.2003pmc: PMC156536pubmed: 12791891google scholar: lookup
              5. Vannella KM, Moore BB. Viruses as co-factors for the initiation or exacerbation of lung fibrosis.. Fibrogenesis Tissue Repair 2008 Oct 13;1(1):2.
                doi: 10.1186/1755-1536-1-2pmc: PMC2577044pubmed: 19014649google scholar: lookup
              6. Kelly BG, Lok SS, Hasleton PS, Egan JJ, Stewart JP. A rearranged form of Epstein-Barr virus DNA is associated with idiopathic pulmonary fibrosis.. Am J Respir Crit Care Med 2002 Aug 15;166(4):510-3.
                doi: 10.1164/rccm.2103058pubmed: 12186829google scholar: lookup
              7. Stewart JP, Egan JJ, Ross AJ, Kelly BG, Lok SS, Hasleton PS, Woodcock AA. The detection of Epstein-Barr virus DNA in lung tissue from patients with idiopathic pulmonary fibrosis.. Am J Respir Crit Care Med 1999 Apr;159(4 Pt 1):1336-41.
                doi: 10.1164/ajrccm.159.4.9807077pubmed: 10194186google scholar: lookup
              8. Lok SS, Haider Y, Howell D, Stewart JP, Hasleton PS, Egan JJ. Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice.. Eur Respir J 2002 Nov;20(5):1228-32.
                doi: 10.1183/09031936.02.00272902pubmed: 12449178google scholar: lookup
              9. Mora AL, Woods CR, Garcia A, Xu J, Rojas M, Speck SH, Roman J, Brigham KL, Stecenko AA. Lung infection with gamma-herpesvirus induces progressive pulmonary fibrosis in Th2-biased mice.. Am J Physiol Lung Cell Mol Physiol 2005 Nov;289(5):L711-21.
                doi: 10.1152/ajplung.00007.2005pubmed: 15734789google scholar: lookup
              10. Stoolman JS, Vannella KM, Coomes SM, Wilke CA, Sisson TH, Toews GB, Moore BB. Latent infection by γherpesvirus stimulates profibrotic mediator release from multiple cell types.. Am J Physiol Lung Cell Mol Physiol 2011 Feb;300(2):L274-85.
                doi: 10.1152/ajplung.00028.2010pmc: PMC3043816pubmed: 21036917google scholar: lookup
              11. Vannella KM, Luckhardt TR, Wilke CA, van Dyk LF, Toews GB, Moore BB. Latent herpesvirus infection augments experimental pulmonary fibrosis.. Am J Respir Crit Care Med 2010 Mar 1;181(5):465-77.
                doi: 10.1164/rccm.200905-0798OCpmc: PMC2830399pubmed: 20185751google scholar: lookup
              12. Becker SD, Bennett M, Stewart JP, Hurst JL. Serological survey of virus infection among wild house mice (Mus domesticus) in the UK.. Lab Anim 2007 Apr;41(2):229-38.
                pubmed: 17430622doi: 10.1258/002367707780378203google scholar: lookup
              13. Ehlers B, Küchler J, Yasmum N, Dural G, Voigt S, Schmidt-Chanasit J, Jäkel T, Matuschka FR, Richter D, Essbauer S, Hughes DJ, Summers C, Bennett M, Stewart JP, Ulrich RG. Identification of novel rodent herpesviruses, including the first gammaherpesvirus of Mus musculus.. J Virol 2007 Aug;81(15):8091-100.
                doi: 10.1128/JVI.00255-07pmc: PMC1951306pubmed: 17507487google scholar: lookup
              14. Williams KJ, Maes R, Del Piero F, Lim A, Wise A, Bolin DC, Caswell J, Jackson C, Robinson NE, Derksen F, Scott MA, Uhal BD, Li X, Youssef SA, Bolin SR. Equine multinodular pulmonary fibrosis: a newly recognized herpesvirus-associated fibrotic lung disease.. Vet Pathol 2007 Nov;44(6):849-62.
                doi: 10.1354/vp.44-6-849pubmed: 18039898google scholar: lookup
              15. Wong DM, Belgrave RL, Williams KJ, Del Piero F, Alcott CJ, Bolin SR, Marr CM, Nolen-Walston R, Myers RK, Wilkins PA. Multinodular pulmonary fibrosis in five horses.. J Am Vet Med Assoc 2008 Mar 15;232(6):898-905.
                doi: 10.2460/javma.232.6.898pubmed: 18341449google scholar: lookup
              16. Brack M, Eichberg JW, Heberling RL, Kalter SS. [Experimentally induced herpesvirus SA 8-pneumonia (bronchopneumonia) in Kenya baboons (papio cynocephalus) (author's transl)].. Virchows Arch A Pathol Anat Histol 1981;392(1):81-96.
                doi: 10.1007/BF00430551pubmed: 6269276google scholar: lookup
              17. Love DN. Feline herpesvirus associated with interstitial pneumonia in a kitten.. Vet Rec 1971 Aug 14;89(7):178-81.
                doi: 10.1136/vr.89.7.178pubmed: 4328223google scholar: lookup
              18. Bolin SR, Ridpath JF, Black J, Macy M, Roblin R. Survey of cell lines in the American Type Culture Collection for bovine viral diarrhea virus.. J Virol Methods 1994 Jul;48(2-3):211-21.
                doi: 10.1016/0166-0934(94)90120-1pubmed: 7989438google scholar: lookup
              19. Chomczynski P, Rymaszewski M. Alkaline polyethylene glycol-based method for direct PCR from bacteria, eukaryotic tissue samples, and whole blood.. Biotechniques 2006 Apr;40(4):454, 456, 458.
                pubmed: 16629392doi: 10.2144/000112149google scholar: lookup
              20. Dynon K, Varrasso A, Ficorilli N, Holloway S, Reubel G, Li F, Hartley C, Studdert M, Drummer H. Identification of equine herpesvirus 3 (equine coital exanthema virus), equine gammaherpesviruses 2 and 5, equine adenoviruses 1 and 2, equine arteritis virus and equine rhinitis A virus by polymerase chain reaction.. Aust Vet J 2001 Oct;79(10):695-702.
                doi: 10.1111/j.1751-0813.2001.tb10674.xpubmed: 11712710google scholar: lookup
              21. Nordengrahn A, Merza M, Ros C, Lindholmc A, Palfl V, Hannant D, Belák S. Prevalence of equine herpesvirus types 2 and 5 in horse populations by using type-specific PCR assays.. Vet Res 2002 May-Jun;33(3):251-9.
                doi: 10.1051/vetres:2002013pubmed: 12056476google scholar: lookup
              22. Kleiboeker SB, Schommer SK, Johnson PJ, Ehlers B, Turnquist SE, Boucher M, Kreeger JM. Association of two newly recognized herpesviruses with interstitial pneumonia in donkeys (Equus asinus).. J Vet Diagn Invest 2002 Jul;14(4):273-80.
                doi: 10.1177/104063870201400401pubmed: 12152805google scholar: lookup
              23. Rovnak J, Quackenbush SL, Reyes RA, Baines JD, Parrish CR, Casey JW. Detection of a novel bovine lymphotropic herpesvirus.. J Virol 1998 May;72(5):4237-42.
                pmc: PMC109653pubmed: 9557713doi: 10.1128/JVI.72.5.4237-4242.1998google scholar: lookup
              24. VanDevanter DR, Warrener P, Bennett L, Schultz ER, Coulter S, Garber RL, Rose TM. Detection and analysis of diverse herpesviral species by consensus primer PCR.. J Clin Microbiol 1996 Jul;34(7):1666-71.
                pmc: PMC229091pubmed: 8784566doi: 10.1128/JCM.34.7.1666-1671.1996google scholar: lookup
              25. Junqueira LC, Bignolas G, Brentani RR. Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections.. Histochem J 1979 Jul;11(4):447-55.
                doi: 10.1007/BF01002772pubmed: 91593google scholar: lookup
              26. SWEAT F, PUCHTLER H, ROSENTHAL SI. SIRIUS RED F3BA AS A STAIN FOR CONNECTIVE TISSUE.. Arch Pathol 1964 Jul;78:69-72.
                pubmed: 14150734
              27. Doran P, Egan JJ. Herpesviruses: a cofactor in the pathogenesis of idiopathic pulmonary fibrosis?. Am J Physiol Lung Cell Mol Physiol 2005 Nov;289(5):L709-10.
                doi: 10.1152/ajplung.00235.2005pubmed: 16214821google scholar: lookup
              28. Egan JJ, Woodcock AA, Stewart JP. Viruses and idiopathic pulmonary fibrosis.. Eur Respir J 1997 Jul;10(7):1433-7.
                doi: 10.1183/09031936.97.10071433pubmed: 9230225google scholar: lookup
              29. Lok SS, Egan JJ. Viruses and idiopathic pulmonary fibrosis.. Monaldi Arch Chest Dis 2000 Apr;55(2):146-50.
                pubmed: 10949877
              30. Pulkkinen V, Salmenkivi K, Kinnula VL, Sutinen E, Halme M, Hodgson U, Lehto J, Jääskeläinen A, Piiparinen H, Kere J, Lautenschlager I, Lappalainen M, Myllärniemi M. A novel screening method detects herpesviral DNA in the idiopathic pulmonary fibrosis lung.. Ann Med 2012 Mar;44(2):178-86.
                pubmed: 21254895doi: 10.3109/07853890.2010.532151google scholar: lookup
              31. Bell SA, Balasuriya UB, Gardner IA, Barry PA, Wilson WD, Ferraro GL, MacLachlan NJ. Temporal detection of equine herpesvirus infections of a cohort of mares and their foals.. Vet Microbiol 2006 Sep 10;116(4):249-57.
                doi: 10.1016/j.vetmic.2006.05.002pubmed: 16774810google scholar: lookup
              32. Wang L, Raidal SL, Pizzirani A, Wilcox GE. Detection of respiratory herpesviruses in foals and adult horses determined by nested multiplex PCR.. Vet Microbiol 2007 Mar 31;121(1-2):18-28.
                doi: 10.1016/j.vetmic.2006.11.009pubmed: 17208393google scholar: lookup
              33. Barton E, Mandal P, Speck SH. Pathogenesis and host control of gammaherpesviruses: lessons from the mouse.. Annu Rev Immunol 2011;29:351-97.
                doi: 10.1146/annurev-immunol-072710-081639pubmed: 21219186google scholar: lookup
              34. Hughes DJ, Kipar A, Sample JT, Stewart JP. Pathogenesis of a model gammaherpesvirus in a natural host.. J Virol 2010 Apr;84(8):3949-61.
                doi: 10.1128/JVI.02085-09pmc: PMC2849519pubmed: 20130062google scholar: lookup
              35. Zinkernagel RM, Hengartner H. Protective 'immunity' by pre-existent neutralizing antibody titers and preactivated T cells but not by so-called 'immunological memory'.. Immunol Rev 2006 Jun;211:310-9.
                doi: 10.1111/j.0105-2896.2006.00402.xpubmed: 16824138google scholar: lookup
              36. Mora AL, Torres-González E, Rojas M, Xu J, Ritzenthaler J, Speck SH, Roman J, Brigham K, Stecenko A. Control of virus reactivation arrests pulmonary herpesvirus-induced fibrosis in IFN-gamma receptor-deficient mice.. Am J Respir Crit Care Med 2007 Jun 1;175(11):1139-50.
                doi: 10.1164/rccm.200610-1426OCpmc: PMC1899276pubmed: 17363768google scholar: lookup
              37. Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.. Am J Respir Crit Care Med 1998 Jan;157(1):199-203.
                doi: 10.1164/ajrccm.157.1.9704130pubmed: 9445300google scholar: lookup
              38. Nicholson AG. Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup.. Histopathology 2002 Nov;41(5):381-91.
                doi: 10.1046/j.1365-2559.2002.01421.xpubmed: 12405906google scholar: lookup
              39. Nicholson AG, Fulford LG, Colby TV, du Bois RM, Hansell DM, Wells AU. The relationship between individual histologic features and disease progression in idiopathic pulmonary fibrosis.. Am J Respir Crit Care Med 2002 Jul 15;166(2):173-7.
                doi: 10.1164/rccm.2109039pubmed: 12119229google scholar: lookup
              40. Collard HR, King TE Jr. Demystifying idiopathic interstitial pneumonia.. Arch Intern Med 2003 Jan 13;163(1):17-29.
                doi: 10.1001/archinte.163.1.17pubmed: 12523913google scholar: lookup
              41. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.. Am J Respir Crit Care Med 1998 Apr;157(4 Pt 1):1301-15.
                doi: 10.1164/ajrccm.157.4.9707039pubmed: 9563754google scholar: lookup
              42. Phan SH. Genesis of the myofibroblast in lung injury and fibrosis.. Proc Am Thorac Soc 2012 Jul;9(3):148-52.
                doi: 10.1513/pats.201201-011AWpmc: PMC5830705pubmed: 22802289google scholar: lookup
              43. Sivakumar P, Ntolios P, Jenkins G, Laurent G. Into the matrix: targeting fibroblasts in pulmonary fibrosis.. Curr Opin Pulm Med 2012 Sep;18(5):462-9.
                doi: 10.1097/MCP.0b013e328356800fpubmed: 22847104google scholar: lookup
              44. Egan JJ, Stewart JP, Hasleton PS, Arrand JR, Carroll KB, Woodcock AA. Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis.. Thorax 1995 Dec;50(12):1234-9.
                doi: 10.1136/thx.50.12.1234pmc: PMC1021343pubmed: 8553293google scholar: lookup
              45. Lok SS, Stewart JP, Kelly BG, Hasleton PS, Egan JJ. Epstein-Barr virus and wild p53 in idiopathic pulmonary fibrosis.. Respir Med 2001 Oct;95(10):787-91.
                doi: 10.1053/rmed.2001.1152pubmed: 11601742google scholar: lookup
              46. Malizia AP, Keating DT, Smith SM, Walls D, Doran PP, Egan JJ. Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGFbeta1 expression.. Am J Physiol Lung Cell Mol Physiol 2008 Sep;295(3):L451-60.
                doi: 10.1152/ajplung.00376.2007pubmed: 18621908google scholar: lookup
              47. Malizia AP, Lacey N, Walls D, Egan JJ, Doran PP. CUX1/Wnt signaling regulates epithelial mesenchymal transition in EBV infected epithelial cells.. Exp Cell Res 2009 Jul 1;315(11):1819-31.
                doi: 10.1016/j.yexcr.2009.04.001pubmed: 19361498google scholar: lookup
              48. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis.. J Clin Invest 2003 Dec;112(12):1776-84.
                doi: 10.1172/JCI20530pmc: PMC297008pubmed: 14679171google scholar: lookup
              49. Willis BC, duBois RM, Borok Z. Epithelial origin of myofibroblasts during fibrosis in the lung.. Proc Am Thorac Soc 2006 Jun;3(4):377-82.
                doi: 10.1513/pats.200601-004TKpmc: PMC2658689pubmed: 16738204google scholar: lookup
              50. Castriotta RJ, Eldadah BA, Foster WM, Halter JB, Hazzard WR, Kiley JP, King TE Jr, Horne FM, Nayfield SG, Reynolds HY, Schmader KE, Toews GB, High KP. Workshop on idiopathic pulmonary fibrosis in older adults.. Chest 2010 Sep;138(3):693-703.
                doi: 10.1378/chest.09-3006pmc: PMC4694103pubmed: 20822991google scholar: lookup
              51. Raghu G, Nyberg F, Morgan G. The epidemiology of interstitial lung disease and its association with lung cancer.. Br J Cancer 2004 Aug;91 Suppl 2(Suppl 2):S3-10.
                doi: 10.1038/sj.bjc.6602061pmc: PMC2750810pubmed: 15340372google scholar: lookup
              52. Xu J, Gonzalez ET, Iyer SS, Mac V, Mora AL, Sutliff RL, Reed A, Brigham KL, Kelly P, Rojas M. Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice.. J Gerontol A Biol Sci Med Sci 2009 Jul;64(7):731-9.
                pmc: PMC2844132pubmed: 19359440doi: 10.1093/gerona/glp040google scholar: lookup
              53. Naik PN, Horowitz JC, Moore TA, Wilke CA, Toews GB, Moore BB. Pulmonary fibrosis induced by γ-herpesvirus in aged mice is associated with increased fibroblast responsiveness to transforming growth factor-β.. J Gerontol A Biol Sci Med Sci 2012 Jun;67(7):714-25.
                doi: 10.1093/gerona/glr211pmc: PMC3391066pubmed: 22193547google scholar: lookup
              54. Torres-González E, Bueno M, Tanaka A, Krug LT, Cheng DS, Polosukhin VV, Sorescu D, Lawson WE, Blackwell TS, Rojas M, Mora AL. Role of endoplasmic reticulum stress in age-related susceptibility to lung fibrosis.. Am J Respir Cell Mol Biol 2012 Jun;46(6):748-56.
                doi: 10.1165/rcmb.2011-0224OCpmc: PMC3380287pubmed: 22227563google scholar: lookup
              55. Flaño E, Husain SM, Sample JT, Woodland DL, Blackman MA. Latent murine gamma-herpesvirus infection is established in activated B cells, dendritic cells, and macrophages.. J Immunol 2000 Jul 15;165(2):1074-81.
                pubmed: 10878386doi: 10.4049/jimmunol.165.2.1074google scholar: lookup
              56. Stewart JP, Usherwood EJ, Ross A, Dyson H, Nash T. Lung epithelial cells are a major site of murine gammaherpesvirus persistence.. J Exp Med 1998 Jun 15;187(12):1941-51.
                doi: 10.1084/jem.187.12.1941pmc: PMC2212355pubmed: 9625754google scholar: lookup
              57. Sunil-Chandra NP, Efstathiou S, Nash AA. Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo.. J Gen Virol 1992 Dec;73 ( Pt 12):3275-9.
                doi: 10.1099/0022-1317-73-12-3275pubmed: 1469366google scholar: lookup
              58. Weck KE, Kim SS, Virgin HW IV, Speck SH. Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells.. J Virol 1999 Apr;73(4):3273-83.
                pmc: PMC104091pubmed: 10074181doi: 10.1128/JVI.73.4.3273-3283.1999google scholar: lookup
              59. Marenzoni ML, Passamonti F, Lepri E, Cercone M, Capomaccio S, Cappelli K, Felicetti M, Coppola G, Coletti M, Thiry E. Quantification of Equid herpesvirus 5 DNA in clinical and necropsy specimens collected from a horse with equine multinodular pulmonary fibrosis.. J Vet Diagn Invest 2011 Jul;23(4):802-6.
                doi: 10.1177/1040638711407890pubmed: 21908328google scholar: lookup

              Citations

              This article has been cited 30 times.
              1. Miglinci L, Reicher P, Nell B, Koch M, Jindra C, Brandt S. Detection of Equine Papillomaviruses and Gamma-Herpesviruses in Equine Squamous Cell Carcinoma. Pathogens 2023 Jan 23;12(2).
                doi: 10.3390/pathogens12020179pubmed: 36839451google scholar: lookup
              2. Acevedo HD, Hassebroek AM, Leventhal HR, Duhamel GE, Carvallo FR. Colonic T-cell-rich, large B-cell lymphoma associated with equid herpesvirus 5 infection and secondary trans-colonic fistula in a horse. J Vet Diagn Invest 2023 May;35(3):272-277.
                doi: 10.1177/10406387231155414pubmed: 36786313google scholar: lookup
              3. Rahman A, Uzal FA, Hassebroek AM, Carvallo FR. Retrospective study of pneumonia in non-racing horses in California. J Vet Diagn Invest 2022 Jul;34(4):587-593.
                doi: 10.1177/10406387221094273pubmed: 35535386google scholar: lookup
              4. El-Hage C, Mekuria Z, Dynon K, Hartley C, McBride K, Gilkerson J. Association of Equine Herpesvirus 5 with Mild Respiratory Disease in a Survey of EHV1, -2, -4 and -5 in 407 Australian Horses. Animals (Basel) 2021 Nov 30;11(12).
                doi: 10.3390/ani11123418pubmed: 34944194google scholar: lookup
              5. Kawano-Dourado L, Glassberg MK, Assayag D, Borie R, Johannson KA. Sex and gender in interstitial lung diseases. Eur Respir Rev 2021 Dec 31;30(162).
                doi: 10.1183/16000617.0105-2021pubmed: 34789464google scholar: lookup
              6. Maboni G, Kelly EJ, Clancy CS, De Luca E, Baldwin TJ, Van Wettere AJ, Kane AJ, Peterson S, Warr VG, Bastian DA, Sanchez S. Detection of asinine gammaherpesviruses in association with pulmonary fibrosis in free-ranging donkeys. J Vet Diagn Invest 2022 Jan;34(1):167-171.
                doi: 10.1177/10406387211052998pubmed: 34689632google scholar: lookup
              7. Duckworth A, Longhurst HJ, Paxton JK, Scotton CJ. The Role of Herpes Viruses in Pulmonary Fibrosis. Front Med (Lausanne) 2021;8:704222.
                doi: 10.3389/fmed.2021.704222pubmed: 34368196google scholar: lookup
              8. Stasiak K, Dunowska M, Trewick S, Rola J. Genetic Variation in the Glycoprotein B Sequence of Equid Herpesvirus 5 among Horses of Various Breeds at Polish National Studs. Pathogens 2021 Mar 9;10(3).
                doi: 10.3390/pathogens10030322pubmed: 33803246google scholar: lookup
              9. Carrillo MF, Kemper D, Woods LW, Carvallo FR. Chronic interstitial pneumonia with features of organizing pneumonia in an adult horse. J Vet Diagn Invest 2020 Jul;32(4):621-625.
                doi: 10.1177/1040638720936251pubmed: 32687009google scholar: lookup
              10. Abade dos Santos FA, Monteiro M, Pinto A, Carvalho CL, Peleteiro MC, Carvalho P, Mendonça P, Carvalho T, Duarte MD. First description of a herpesvirus infection in genus Lepus. PLoS One 2020;15(4):e0231795.
                doi: 10.1371/journal.pone.0231795pubmed: 32302375google scholar: lookup
              11. Dall Agnol AM, Beuttemmuller EA, Pilz D, Leme RA, Saporiti V, Headley SA, Alfieri AF, Alfieri AA. Detection of Equid gammaherpesvirus 2 and 5 DNA in the upper respiratory tract of asymptomatic horses from Southern Brazil. Braz J Microbiol 2019 Jul;50(3):875-878.
                doi: 10.1007/s42770-019-00100-7pubmed: 31187445google scholar: lookup
              12. Hendrikse LD, Kambli A, Kayko C, Canuti M, Rodrigues B, Stevens B, Vashon J, Lang AS, Needle DB, Troyer RM. Identification of a Novel Gammaherpesvirus in Canada lynx (Lynx canadensis). Viruses 2019 Apr 20;11(4).
                doi: 10.3390/v11040363pubmed: 31010021google scholar: lookup
              13. Van Cleemput J, Poelaert KCK, Laval K, Nauwynck HJ. Unravelling the first key steps in equine herpesvirus type 5 (EHV5) pathogenesis using ex vivo and in vitro equine models. Vet Res 2019 Feb 18;50(1):13.
                doi: 10.1186/s13567-019-0630-6pubmed: 30777128google scholar: lookup
              14. Sorel O, Dewals BG. The Critical Role of Genome Maintenance Proteins in Immune Evasion During Gammaherpesvirus Latency. Front Microbiol 2018;9:3315.
                doi: 10.3389/fmicb.2018.03315pubmed: 30687291google scholar: lookup
              15. Easton-Jones CA, Madigan JE, Barnum S, Maxwell LK, Taylor SD, Arnesen T, Pusterla N. Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular pulmonary fibrosis. J Vet Intern Med 2018 Sep;32(5):1763-1767.
                doi: 10.1111/jvim.15230pubmed: 30221792google scholar: lookup
              16. Marenzoni ML, Stefanetti V, Danzetta ML, Timoney PJ. Gammaherpesvirus infections in equids: a review. Vet Med (Auckl) 2015;6:91-101.
                doi: 10.2147/VMRR.S39473pubmed: 30155436google scholar: lookup
              17. Smith FL, Watson JL, Spier SJ, Kilcoyne I, Mapes S, Sonder C, Pusterla N. Frequency of shedding of respiratory pathogens in horses recently imported to the United States. J Vet Intern Med 2018 Jul;32(4):1436-1441.
                doi: 10.1111/jvim.15145pubmed: 29761571google scholar: lookup
              18. Tashiro J, Rubio GA, Limper AH, Williams K, Elliot SJ, Ninou I, Aidinis V, Tzouvelekis A, Glassberg MK. Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis. Front Med (Lausanne) 2017;4:118.
                doi: 10.3389/fmed.2017.00118pubmed: 28804709google scholar: lookup
              19. Jenkins RG, Moore BB, Chambers RC, Eickelberg O, Königshoff M, Kolb M, Laurent GJ, Nanthakumar CB, Olman MA, Pardo A, Selman M, Sheppard D, Sime PJ, Tager AM, Tatler AL, Thannickal VJ, White ES. An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis. Am J Respir Cell Mol Biol 2017 May;56(5):667-679.
                doi: 10.1165/rcmb.2017-0096STpubmed: 28459387google scholar: lookup
              20. Moore BB, Moore TA. Viruses in Idiopathic Pulmonary Fibrosis. Etiology and Exacerbation. Ann Am Thorac Soc 2015 Nov;12 Suppl 2(Suppl 2):S186-92.
                doi: 10.1513/AnnalsATS.201502-088AWpubmed: 26595738google scholar: lookup
              21. Brandenberger C, Ochs M, Mühlfeld C. Assessing particle and fiber toxicology in the respiratory system: the stereology toolbox. Part Fibre Toxicol 2015 Oct 31;12:35.
                doi: 10.1186/s12989-015-0110-8pubmed: 26521139google scholar: lookup
              22. Wilkie GS, Kerr K, Stewart JP, Studdert MJ, Davison AJ. Genome sequences of equid herpesviruses 2 and 5. Genome Announc 2015 Mar 12;3(2).
                doi: 10.1128/genomeA.00119-15pubmed: 25767243google scholar: lookup
              23. Stasiak K, Dunowska M, Rola J. Genetic Diversity of Equid Herpesvirus 5 in Temporal Samples from Mares and Their Foals at Three Polish National Studs. Int J Mol Sci 2025 Aug 27;26(17).
                doi: 10.3390/ijms26178298pubmed: 40943220google scholar: lookup
              24. Hardefeldt L, Thomas K, Page S, Norris J, Browning G, El Hage C, Stewart A, Gilkerson J, Muscatello G, Verwilghen D, van Galen G, Bauquier J, Cuming R, Reynolds B, Whittaker C, Wilkes E, Clulow J, Burden C, Begg L. Antimicrobial prescribing guidelines for horses in Australia. Aust Vet J 2025 Dec;103(12):781-889.
                doi: 10.1111/avj.70003pubmed: 40903020google scholar: lookup
              25. Gilbert M, Hill MAM, Cheung LYN, Kiser PK, Seryodkin IV, Miquelle DG, Goodrich JM, Sulikhan N, Uphyrkina O, Goncharuk M, Kerley L, Troyer RM. Predator-prey transmission of a gammaherpesvirus from Asian badgers (Meles leucurus) to endangered Amur tigers (Panthera tigris altaica). PLoS One 2025;20(7):e0327463.
                doi: 10.1371/journal.pone.0327463pubmed: 40601710google scholar: lookup
              26. Sung JS, Ko IG, Hwang L, Kim SH, Han JH, Jeon JW, Kim SR, Lee JM, Choi CW. Pirfenidone Alleviates Against Fine Particulate Matter-Induced Pulmonary Fibrosis Modulating via TGF-β1/TAK1/MKK3/p38 MAPK Signaling Pathway in Rats. Biomedicines 2025 Apr 17;13(4).
                doi: 10.3390/biomedicines13040989pubmed: 40299673google scholar: lookup
              27. Pöpperl P, Stoff M, Beineke A. Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense. Int J Mol Sci 2025 Jan 5;26(1).
                doi: 10.3390/ijms26010407pubmed: 39796262google scholar: lookup
              28. Shadid A, Rich HE, DeVaughn H, Domozhirov A, Doursout MF, Weng-Mills T, Eckel-Mahan KL, Karmouty-Quintana H, Restrepo MI, Shivshankar P. Persistent microbial infections and idiopathic pulmonary fibrosis - an insight into non-typeable Haemophilus influenza pathogenesis. Front Cell Infect Microbiol 2024;14:1479801.
                doi: 10.3389/fcimb.2024.1479801pubmed: 39760094google scholar: lookup
              29. Craven A, Todd-Donato A, Stokol T, Liepman R, Glasberg I, Wilkins P, Luethy D, Wong D, Schoster A, van den Brom-Spierenburg AJ, Tomlinson JE. Clinical findings and outcome predictors for multinodular pulmonary fibrosis in horses: 46 cases (2009-2019). J Vet Intern Med 2024 May-Jun;38(3):1842-1857.
                doi: 10.1111/jvim.17084pubmed: 38619130google scholar: lookup
              30. Bianchessi L, Flach E, Monacchia G, Dagleish M, Maley M, Turin L, Rocchi MS. Identification and characterisation of Gamma-herpesviruses in zoo artiodactyla. Virol J 2024 Feb 23;21(1):49.
                doi: 10.1186/s12985-024-02311-3pubmed: 38395934google scholar: lookup
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