General and Ophthalmic Manifestations of Herpes Virus Infections

Herpes viruses are a large group of DNA viruses causing a wide variety of diseases in humans. The exponential growth of medicine in general and advanced achievements of virology in particular authentically verified a wide spectrum of diseases in humans caused by or associated with herpesvirus infections. Eight types of herpes viruses particularly human simplex type 1 and 2, varicella-zoster, Epstein-Barr, cytomegalovirus, roseoloviruses type 6 and 7, and Kaposi’s sarcoma-associated herpesvirus were described in the article. This overview highlights the main issues of worldwide epidemiology, basic virology and clinical manifestations of herpes virusesinduced diseases and associated conditions, including general and ophthalmic disorders. Their prevalence in the world accounts for the almost the entire population. The majority human herpes viruses are typically acquired in infancy or early adulthood as a primary disease, and infect neurons, lymphoid or epithelial cells to persist for life and establish a latent infection. Reactivated human herpes viruses may present different clinical pictures and induce a broad spectrum of illnesses ranging from asymptomatic carrier state to recurrent life-threatening conditions and fatal diseases, especially in immunocompromised patients. This review particularly highlights the description of the diseases affecting the eye: anterior and posterior herpes-associated uveitis and acute retinal necrosis. Clinically herpes viruses can manifest in a variety of eye symptoms and signs complicating the diagnosis. Viral DNA in the eye mediums and tissues detection by means of PCR seems to be a challenge for practitioners. Thus, the review of latest research and developments indicate the need for newer diagnostic and management approaches to counter the herpes virus infectious.

herpes viruses, herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, roseolovirus, uveitis, retinal necrosis, polymerase chain reaction

1. Johnson R.W., Alvarez-Pasquin M.J., Bijl M., Franco E., Gaillat J., Clara J.G., Labetoulle M., Michel J.P., Naldi L., Sanmarti L.S., Weinke T. Herpes zoster epidemiology, management, and disease and economic burden in Europe: a multidisciplinary perspective. Therapeutic Advances in Vaccines. 2015;3(4):109–120. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591524/ (10.11.2016).

2. Liesegang T.J. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115 (2 Suppl):S3–12.

3. Van Gelderen B., Van der Lelij A., Treffers W., Van der Gaag R. Detection of herpes simplex virus type 1, 2 and varicella zoster virus DNA in recipient corneal buttons British Journal of Ophthalmology. 2000;84:1238–1243. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1723286/pdf/v084p01238.pdf (10.11.2016).

4. Pitkaranta A., Piiparinen H., Mannonen L., Vesaluoma M., Vaheri, A. Detection of human herpesvirus 6 and varicella-zoster virus in tear fluid of patients with Bell’s palsy by PCR. Journal of Clinical Microbiology. 2000;38:2753–2755.URL: http://jcm.asm.org/content/38/7/2753.full (10.11.2016 ).

5. Gilden D., Nagel M., Cohrs R., Mahalingam R., Baird N. Varicella zoster virus in the nervous system. F1000Research 2015; 4: 1356. URL: http://f1000researchdata.s3.amazonaws.com/manuscripts/7707/15baa80b-e08e-437b-965f-2f384e55a776_7153_-_don_gilden.pdf (10.11.2016).

6. De Broucker T., Mailles A., Chabrier S., Morand P. and Stahl J. (2012) Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case series of 20 patients. Clinical Microbiology and Infection. 2012;18(8):808–819.

7. Aoki Y., Iwamoto M., Kimura H., Nagashima T., Yoshio T., Okazaki H., Minota S. The incidence of infectious complications during admission and within 2 months after discharge in patients with systemic lupus erythematosus treated with high dose glucocorticoids. Jichi Medical University Journal. 2007; 30: 29–36. URL http://www.jichi.ac.jp/lib/jmu-kiyo/30/kjP29-36.pdf (10.11.2016).

8. Che H., Lukas C., Morel J. and Combe B. Risk of herpes/herpes zoster during antitumor necrosis factor therapy in patients with rheumatoid arthritis. Systematic review and meta-analysis. Joint Bone Spine. 2014;81(3):215–221.

9. Chen M.H., Wei H.T., Su T.P., Li C.T., Lin W.C., Chang W.H., Chen T.J., Bai Y.M. Risk of depressive disorder among patients with herpes zoster: a nationwide population-based prospective study. Psychosomatic Medicine. 2014;76(4):285–291.

10. Huygens A., Dauby N., Vermijlen D., Marchant A. Immunity to Cytomegalovirus in Early Life. Frontiers in Immunology. 2014; 5: 552. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214201/ (10.11.2016).

11. Ludwig A., Hengel H. Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe. European Surveillance. 2009;14(9):26–32. URL: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19140 (10.11.2016).

12. Hanley P.J., Bollard C.M. Controlling cytomegalovirus: Helping the immune system take the lead. Viruses 2014; 6 (6): 2242–2258. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074926/ (10.11.2016).

13. Crough T, Khanna R. Immunobiology of human cytomegalovirus: from bench to bedside. Clinical Microbiology Reviews. 2009; 22 (1): 76–98. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2620639/ (10.11.2016).

14. Tan B.H. Cytomegalovirus Treatment. Current treatment options in infectious diseases. 2014;6(3):256–270.

15. Squizzato A., Gerdes V.E.A., Buller H.R. Effects of human cytomegalovirus infection on the coagulation system. Thrombosis and Haemostasis. 2005;93(3):403–410.

16. Tichelaar V.Y., Sprenger H.G., Makelburg A.B., Niesters B.G., Kluin-Nelemans H.C., Lijfering W.M. Active cytomegalovirus infection in patients with acute venous thrombosis: a case-control study. American Journal of Hematology. 2011; 86 (6): 510–512. URL: http://onlinelibrary.wiley.com/doi/10.1002/ajh.22006/pdf (10.11.2016).

17. Halenius A., Hengel H. Human cytomegalovirus and autoimmune disease. BioMed Research International. 2014 [Электронный ресурс]. URL: https://www.hindawi.com/journals/bmri/2014/472978/ (10.11.2016).

18. Kanetaka Y., Kano Y., Hirahara K., Kurata M., Shiohara T. Relationship between cytomegalovirus reactivation and dermatomyositis. European Journal of Dermatology. 2011;21(2):248–253.

19. Shi1 X.L., de Mare-Bredemeijer E.L., Tapirdamaz Ц., Hansen B.E., van Gent R., van Campenhout M.J., Mancham S., Litjens N.H., Betjes M.G., van der Eijk A.A., Xia Q., van der Laan L.J., de Jonge J., Metselaar H.J., Kwekkeboom J. CMV primary infection is associated with donor-specific T cell hyporesponsiveness and fewer late acute rejections after liver transplantation. American Journal of Transplantation. 2015;15(9):2431–2442. URL: http://onlinelibrary.wiley.com/doi/10.1111/ajt.13288/epdf (10.11.2016).

20. Requiгo-Moura L.R., Carvalho de Matos A.C., Pacheco-Silva A. Cytomegalovirus infection in renal transplantation: clinical aspects, management and the perspectives. Einstein. 2015; 13 (1): 142–148. URL: http://www.scielo.br/pdf/eins/v13n1/1679-4508-eins-13-1-142.pdf (10.11.2016).

21. Pawelec G., McElhaney J.E., Aiello A.E., Derhovanessian E. The impact of CMV infection on survival in older humans. Current Opinion in Immunology. 2012; 24: 507–511. URL: http://www.ideal-ageing.eu/uploads/publicaties/2012/2012_pawelec_curropinimmunol.pdf (10.11.2016).

22. Cobbs C.S. Cytomegalovirus and brain tumor: epidemiology, biology and therapeutic aspects. Current Opinion on Oncology. 2013;25:682–688.

23. Miller D.M., Espinosa-Heidmann D.G., Legra J., Dubovy S.R., Suner I.J., Sedmak D.D., Dix R.D., Cousins S.W. The association of prior cytomegalovirus infection with neovascular agerelated macular degeneration. American Journal of Ophthalmology.2004;138:323–328.

24. Cousins S.W., Espinosa-Heidmann D.G., Miller D.M., Pereira-Simon S., Hernandez E.P., Chien H., Meier-Jewett C., Dix R.D. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization. PLOS Pathogens. 2012; 8 (4): e1002671 [Электронный ресурс]. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343109/pdf/ppat.1002671.pdf (10.11.2016).

25. Dunmire S.K., Hogquist K.A., Balfour H.H. Jr. Infectious mononucleosis. Current Topics in Microbiology and Immunology. 2015; 390: 211–240. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670567/ (10.11.2016).

26. Ali A.S., Al-Shraim M., Al-Hakami A.M., Jones I.M. Epstein- Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis. The Open Virology Journal. 2015; 9: 7–28. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740969/ (10.11.2016).

27. Miller G. The oncogenicity of Epstein-Barr virus. The Journal of Infectious Diseases. 1974;130(2):187–205.

28. Feederle R., Bartlett E.J., Delecluse H.J. Epstein-Barr virus genetics: talking about the BAC generation. Herpesviridae. 2010; 1 (1): 6. URL: https://www.ncbi.nlm.nih. gov/pmc/articles/PMC3063228/ (10.11.2016).

29. Allan G.J., Inman G.J., Parker B.D., Rowe D.T., Farrell P.J. Cell growth effects of Epstein-Barr virus leader protein. Journal of General Virology. 1992;73(6):1547–1551. URL: http://www.microbiologyresearch.org/docserver/fulltext/jgv/73/6/JV0730061547.pdf?expires=1479089087&id=id&accname=guest&checksum=6F04785D507C5979F112E5394A65A445 (10.11.2016).

30. Gonzalez-Moles M.A., Gutierrez J., Rodriguez M.J., Ruiz-Avila I., Rodriguez-Archilla A. Epstein-Barr virus latent membrane protein-1 (LMP-1) expression in oral squamous cell carcinoma. Laryngoscope. 2002;112(3):482–487.

31. Khammissa R.A.G., Fourie J., Chandran R., Lemmer J., Feller. Epstein-Barr virus and its association with oral hairy leukoplakia: a short review. International Journal of Dentistry. 2016 [Электронный ресурс]. URL: https://www.hindawi.com/journals/ijd/2016/4941783/ (10.11.2016).

32. Geng L., Wang X. Epstein-Barr Virus-associated lymphoproliferative disorders: experimental and clinical developments. International Journal of Clinical and Experimental Medicine. 2015; 8 (9): 14656–14671. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658837/ (10.11.2016).

33. Yang X., Nishida N., Zhao X., Kanegane H. Advances in understanding the pathogenesis of Epstein-Barr virus-associated lymphoproliferative disorders. Iranian Journal of Allergy, Asthma and Immunology. 2015; 14 (5): 462–471. URL: http://ijaai.tums.ac.ir/index.php/ijaai/article/view/595 (10.11.2016).

34. Shinozaki-Ushiku A., Kunita A., Fukayama M. Update on Epstein-Barr virus and gastric cancer (review). International Journal of Oncology. 2015; 46 (4): 1421–1434. URL: https://www.spandidos-publications.com/ijo/46/4/1421 (10.11.2016).

35. Vйgso G., Hajdu M., Sebestyйn A. Lymphoproliferative disorders after solid organ transplantation-classification, incidence, risk factors, early detection and treatment options. Pathology and Oncology Research. 2011;17(3):443–454.

36. Looker K., Garnett G. A systematic review of the epidemiology and interaction of herpes simplex virus types 1 and 2. Sexually Transmitted Infections. 2005; 81 (2): 103–107. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764655/pdf/v081p00103.pdf (10.11.2016).

37. Tan Ik.L., McArthur J.C., Venkatesan A., Nath A. Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology. 2012;79 (21):2125–2132. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511927/ (10.11.2016).

38. Chong S., Kim T.S., Cho E.Y. Herpes simplex virus pneumonia: high-resolution CT findings. The British Journal of Radiology. 2010;83(991):585–589. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473669/ (10.11.2016).

39. Norvell J.P., Blei A.T., Jovanovic B.D., Levitsky J. Herpes simplex virus hepatitis: An analysis of the published literature and institutional cases. Liver transplantation. 2007;13(10):1428–1434.

40. Cripe T.P., Chen C.Y., Denton N.L., Haworth K.B., Hutzen B., Leddon J.L., Streby K.A., Wang P.Y., Markert J.M., Waters A.M., Gillespie G.Y., Beierle E.A., Friedman G.K. Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children. Molecular Therapy — Oncolytics. 2015; 2: 15015 [Электронный ресурс]. URL: http://www.nature.com/articles/mto201515 (10.11.2016).

41. Ge X., Wang X., Shen P. Herpes simplex virus type 2 or human herpesvirus 8 infection and prostate cancer risk: A meta-analysis. Biomedical reports. 2013; 1 (3): 433–439. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917040/(10.11.2016).

42. Harris S.A., Harris E.A. Herpes simplex virus type 1 and other pathogens are key causative factors in sporadic Alzheimer’s disease. Journal of Alzheimer’s Disease. 2015; 48 (2): 319–353. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923765/ (10.11.2016).

43. Haeseker M.B., Pijpers E., Dukers-Muijrers N.H.T.M., Nelemans P., Hoebe C.J.P.A., Bruggeman C.A., Verbon A., Goossens VJ. Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study. Immunity &Ageing. 2013, 10:30 [Электронный ресурс]. URL: http://download.springer.com/static/pdf/175/art%253A10.1186%252F1742-4933-10-30.pdf?originUrl=http%3A%2F%2Fimmunityageing.biomedcentral.com%2Farticle%2F10.1186%2F1742-4933-10-30&token2=exp=1479090354~acl=%2Fstatic%2Fpdf%2F175%2Fart%25253A10.1186%25252F1742-4933-10-30.pdf*~hmac=3f4ce6dda4b4d920163f3fb576fc739d9bfd64fa9a134b8e0062a639d00d5f52 (10.11.2016).

44. Komaroff A.L., Phan T., Flamand L., Pellett P.E. Summary of the 9th International Conference on Human herpesviruses 6 and 7 (HHV-6A, HHV-6B and HHV-7). Journal of Medical Virology. 2016; 88 (12): 2038–2043. URL: http://onlinelibrary.wiley.com/doi/10.1002/jmv.24561/epdf (10.11.2016).

45. Chuh A., Zawar V., Sciallis G.F., Kempf W., Lee A. Pityriasis rosea, Gianotti-Crosti syndrome, asymmetric periflexural exanthem, papular-purpuric gloves and socks syndrome, eruptive pseudoangiomatosis, and eruptive hypomelanosis: Do their epidemiological data substantiate infectious etiologies? Infectious Disease Reports. 2016; 8 (1): 6418 [Электронный ресурс]. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815944/ (10.11.2016).

46. Ishida T., Kano Y., Mizukawa Y., Shiohara T. The dynamics of herpesvirus reactivations during and after severe drug eruptions: their relation to the clinical phenotype and therapeutic outcome. Allergy. 2014; 69 (6): 798–805. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112819/ (10.11.2016).

47. Shimanovsky A., Patel D., Wasser J. Refractory immune thrombocytopenic purpura and cytomegalovirus infection: a call for a change in the current guidelines. Mediterranean Journal of Hematology and Infectious Diseases. 2016; 8 (1): 2016010 [Электронный ресурс]. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696470/ (10.11.2016).

48. Dittmer D.P., Damania B. Kaposi sarcoma-associated herpesvirus: immunobiology, oncogenesis, and therapy. Journal of Clinical Investigation. 2016; 126(9): 3165–3175.

49. Ingianni A., Piras E., Laconi S., Angius F., Batetta B., Pompei R. Latent herpesvirus 8 infection improves both insulin and glucose uptake in primary endothelial cells. New Microbiologica. 2013; 36: 257–265. URL: http://www.academia.edu/25115329/Latent_Herpesvirus_8_infection_improves_both_insulin_and_glucose_uptake_in_primary_endothelial_cells (10.11.2016).

50. Pompei R. The role of human herpesvirus 8 in diabetes mellitus type 2: state of the art and a medical hypothesis. Advances in Experimental Medicine and Biology —Advances in Microbiology, Infectious Diseases and Public Health. 2016; 901: 37–45.

51. International Uveitis Study Group (IUSG) [Электронный ресурс]. URL: http://www.iusg.net/ (10.11.2016).

52. Le T.D., Weisbrod D., Mandelcorn E.D. Chorioretinitis with exudative retinal detachment secondary to varicella zoster virus. Canadian Journal of Ophthalmology. 2015;50 (5):e91–93.

53. Tugal-Tutkun I., Otьk-Yasar B., Altinkurt E. Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases. International Ophthalmology. 2010;30(5):559–565.

54. Chee S.P., Jap A. Immune ring formation associated with cytomegalovirus endotheliitis. American Journal of Ophthalmology. 2011;152(3): 449–453.

55. Pleyer U., Chee S.P. Current aspects on the management of viral uveitis in immunocompetent individuals. Clinical Ophthalmology. 2015; 9: 1017–1028. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467646/ (10.11.2016).

56. Chee S.P., Bacsal K., Jap A., Se-Thoe S.Y., Cheng C.L., Tan B.H. Clinical features of cytomegalovirus anterior uveitis in immunocompetent patients. American Journal of Ophthalmology. 2008;145(5):834–840.

57. Wickremasinghe S.S., Stawell R., Lim L., Pakrou N., Zamir E. Non-necrotizing herpetic vasculitis. Ophthalmology. 2009;116(2):361.

58. Cochrane T.F., Silvestri G., McDowell C., Foot B., McAvoy C.E. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study. Eye. 2012; 26 (3): 370–378. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298997/(10.11.2016).

59. Silva R.A., Berrocal A.M., Moshfeghi D.M., Blumenkranz M.S., Sanislo S., Davis J.L. Herpes simplex virus type 2 mediated acute retinal necrosis in a pediatric population: case series and review. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2013;251(2):559–566.