Human Immune System and Characteristics of Herpetic Infection Pathogenesis (Review)

In recent years the significance of knowledge of immune mechanisms of various pathological conditions is growing, since it is related to the survival peculiarities of modern human. Acute diseases are frequently protracted, the number of chronic conditions increasing. The principal tasks of human immune system study is to determine an impaired component of immunity system, make the prognosis of a chronic character of the disease, and assess the provided treatment efficiency.

Virus immunology is progressing rapidly. However, there are still many incomprehensible mechanisms of interaction between a human organism and viruses; some functions of many virus proteins enabling viruses to escape immune surveillance are understudied. Such studies will enable to comprehend significantly the pathogenesis of virus infections, and therefore develop new forms of treatment and prevention.

The review presents current views on immune response formation in herpetic infection, the interaction mechanisms of a virus and a macroorganism, the main lines of research in a clinical picture, diagnosis and management of the pathology.

1. Akberova S.I., Ershov F.I., Musaev P.I., et al. Dynamics of interferon status in patients with herpetic keratites in the treatment of interferon inducers. Vestnik oftal’mologii 2008; 1: 33–35.
2. Isakov V.A. Modern treatment techniques of herpetic infection. Terra Medica 1997; 3: 2–6.
3. Belyakov I.M., Isakov D., Zhu Q., et al. A novel functional CTL avidity/activity compartmentalization to the site of mucosal immunization contributes to protection of macaques against simian/human immunodeficiency viral depletion of mucosal CD4+ T cells. J Immunology 2007; 178(11): 7211–7221.
4. Katagadze Z.G. Immunodiagnosis and immunotherapy. Vestnik RAMN 1999; 5: 19–22.
5. Belyakov I.M., Kuznetsov V.A., Kelsall B., et al. Impact of vaccine-induced mucosal high avidity CD8+ CTLs in delay of AIDS-viral dissemination from mucosa. Blood 2008; 3258: 3258–3264.
6. Masopust D., Choo D., Vezyes V. Dynamic T-cell migration programmprovides resident memory within intestinal epithelium. J Exp Med 2010; 207(3): 533–564, http://dx.doi.org/10.1084/jem.20090858.
7. Paludan S.R., Bowie A.G., Horan K.A., Fitzgerald K.A. Recognitin of herpesviruses by the innate immune system. Nat Rev Immunol 2011; 11(2): 143–154, http://dx.doi.org/10.1038/nri2937.
8. Wakim L.M., Woodward A., Bevan M.J. Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Nat Acad Sci USA 2010; 107(42): 17872–17879, http://dx.doi.org/10.1073/pnas.1010201107.
9. West J.A., Gregory S.M., Sivaraman V., et al. Activation of plasmacytoid dendritic cells by Kaposi’s sarcoma-associated herpesvirus. J Virol 2011; 85(2): 895–904, http://dx.doi.org/10.1128/JVI.01007-10.
10. Karaulov A.V., Evsegneeva I.V., Tyuleneva E.B. The study of soluble differential antigen content in patients with diabetes mellitus. Rossiyskiy bioterapevticheskiy zhurnal 2006; 1: 75–79.
11. Ballantyne C.M., Kozak C.A., O’Brien W.E., Beaudet A.L. Assignment of the gene for intercellular adhesion molecule-1 (Icam-1) to proximal mouse chromosome 9. Genomics 1991; 9(3): 547–550, http://dx.doi.org/10.1016/0888-7543(91)90423-C.
12. Abdulmedzhieva A.G., Torganova I.G., Vityazeva I.I. The effect of asymptomatic herpes virus infection on the efficiency of infertility treated by assisted reproductive technologies. Akusherstvo i ginekologiya 2009; 1: 45–48.
13. Nosik N.N., Stakhanova V.M. Laboratory diagnosis of viral infections. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya 2000; 2: 70–78.
14. Timchenko V.N., Chernova T.M. Infectious mononucleosis: diagnosis and management problems. Terra Medica 2006; 1: 62–65.
15. Kadagidze Z.G., Zabotina T.N., Korotkova O.V. Current capabilities of using immunologic indices in immunotherapy of oncology patients.Vestnik RONTs im. N.N. Blokhina 1996; 1: 50–55.
16. Barreiro O., Yez-M M., Sala-Valdés M., et al. Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation. Blood 2005; 105(7): 2852–2861.
17. Stepanova E.V. Herpes virus diseases and HIV-infection. VICh-infektsiya i immunosupressiya 2009; 2: 16–30.
18. Fleming D.T., McQuillan G.M., Johnson R.E., et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. NEJM 1997; 16: 1105–1111.
19. Kalugina M.Yu., Karzhas N.V., Kozina V.I., et al. Herpetic infections in patients with immunodeficiency state. Zhurnal mikrobiologii, epidemiologii i immunologii 2009; 1: 79–80.
20. Stepanova E.V., Panteleeva O.V., Rassokhin V.V. Purulent septic and opportunistic diseases in HIV-infection. Vestnik gematologii 2010; 1: 64–65.
21. Novikov V.V., Chesnokova T.V., Monakova E.A. The role of soluble CD38, CD50, CD95 antigens in immune response modulation in cytomegalovirus infection. Palliativnaya meditsina i reabilitatsiya 2005; 1: 75.
22. Adieva A.A., Gadzhieva Z.S., Kask L.N., et al. Polymerase chain reaction in situ to reveal DNA of herpes simplex virus and cytomegalovirus in autopsy materials of fetuses and non-survived newborns. Voprosy diagnostiki v pediatrii 2010; 2(2): 20–25.
23. Bocharova E.N., Kurilo L.F., Shileyko L.V., et al. The analysis of sperm pool in male ejaculate infected by herpes simplex virus. Ontogenez 2008; 1: 47–57.
24. Naumenko V.A., Kushch A.A. Herpes viruses and male infertility: is there any relationship? Voprosy virusologii 2013; 3: 4–8.
25. Gadzhieva Z.S., Tsibizov A.S., Novikova S.V. Detection of herpes viral infection in pregnant women with burdened obstetric history. Sovremennye problemy dermatovenerologii, immunologii i vrachebnoy kosmetologii 2010; 2: 15–21.
26. Kushch A.A., Degtyareva M.V., Malinovskaya V.V., et al. Efficiency of recombinant Interferon α-2 (Viferon) management in premature infants with severe prenatal infections. Detskie infektsii 2009; 3: 40–44.
27. Naumenko V.A., Klimova R.R., Kurilo L.F., et al. Detection of herpes simplex virus in sperm in experimental infection of testis organ culture and infertile male ejaculate. Akusherstvo i ginekologiya 2010; 3: 42–46.
28. Kupaev V.I., Davydkin I.L., Rossiev V.A. Analysis of infectious complications in patients with hemoblastoses. Vestnik gematologii 2010; 1: 41–44.
29. Coen D.V., Schaffer P.A. Antiherpesvirus drugs: a promising spectrum of new drugs and drug targets. Nat Rev Drug Discov 2003; 2(4): 278–288.
30. Dolgikh T.I., Ershov A.V., Minakova E.Yu., Zapariy N.S. Immunologic characteristics of newly diagnosed herpetic infection. Infektsionnye bolezni 2010; 8(1): 25–28.
31. Johnson R.W. Herpes zoster in the immunocompetent patient: management of post-herpetic neuralgia. Herpes 2003; 10(2): 38–45.
32. Raborn G.W., Grace M.G.A. Recurrent herpes simplex labialis: selected therapeutic options. J Can Dental Association 2003; 69(8): 498–502.
33. Braun R.E., Lo D., Pinkert C.A. Infertility in male transgenic mice: disruption of sperm development by HSV-tk expression in postmeiotic germ cells. Biol Reprod 1990; 43(4): 684–693, http://dx.doi.org/10.1095/biolreprod43.4.684.
34. Eggert-Kruse W., Reuland M., Johannsen W., et al. Cytomegalovirus (CMV) infection — related to male and/or female infertility factor? Fertil Steril 2009; 91(1): 67–82, http://dx.doi.org/10.1016/j.fertnstert.2007.11.014.
35. Gribencha S.V., Bragina E.E., Abdumalikov R.A., et al. Detection of type 2 herpes simplex virus in cells of spermatogenic epithelium in infected testes of guinea pigs. Bull Exp Biol Med 2007; 144(1): 73–76.
36. Vaynshenker Yu.I., Kalinina O.V., Nuralova I.V., et al. Minimally clinical perinatal infections and their clinical and neurological manifestations in children and adolescents. Infektsionnye bolezni 2013; 1: 44–49.
37. Hill C., McKinney E., Lowndes C.M., et al. Epidemiology of herpes simplex virus types 2 and 1 amongst men who have sex with men attending sexual health clinics in England and Wales: implications for HIV prevention and management. Euro Surveill 2009; 14(47): 19418.
38. Vyaz’mina E.S., Novikov V.V., Dobrotina N.A., et al. Serum levels of cytokines and soluble membrane antigens of immune cells. Tsitokiny i vospalenie 2002; 1(3): 15–19.
39. Hall C.B., Caserta M.T., Schnabel K., et al. Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics 2008; 122(3): 513–520, http://dx.doi.org/10.1542/peds.2007-2838.
40. Cai L.Y., Kato T., Nakayama M., et al. HSV type 1 thymidine kinase protein accumulation in round spermatids nduces male infertility by spermatogenesis disruption and apoptotic loss of germ cell. Reprod Toxicol 2009; 27(1): 14–21, http://dx.doi.org/10.1016/j.reprotox.2008.11.052.
41. Klimova R.R., Chichiev E.V., Naumenko V.A. Herpes simplex virus and cytomegalovirus in male ejaculate: herpes simplex virus is more common in idiopathic infertility and correlates to decreased semen indices.Voprosy virusologii 2010; 1: 27–31.
42. Abdulmedzhidova A.G., Kurilo A.G., Shileyko L.V., et al. Asymptomatic genital herpes and infertility in men. Urologiya 2007; 3: 56–58.
43. Kapranos N.C., Kotronias D.C. Detection of herpes simplex virus in first trimester pregnancy loss using molecular techniques. In vivo 2009; 23(5): 839–842.
44. Naumenko V.A., Tyulenev Yu.A., Segal A.S., et al. The effect of herpes simplex virus on spermatogenesis. Urologiya 2011; 6: 32–36.
45. Klimova R.R., Naumenko V.A., Kurilo L.F., et al. The effect of herpes simplex virus on mice spermatogenesis in experimental infection of testis fragment organ culture. Andrologiya i genital’naya khirurgiya 2009; 4: 44–49.
46. Kapranos N.C., Petrakou E., Anastasiadou C., Kotronias D. Detection of herpes simplex virus, cytomegalovirus, and Epstein–Barr virus in the semen of men attending an infertility clinic. Fertil Steril 2003; 79(3): 1566–1570, http://dx.doi.org/10.1016/S0015-0282(03)00370-4.
47. Krikun G., Lockwood C.J., Abrahams V.M., et al. Expression of Toll-like receptors in the human decidua. Histol Histopathol 2007; 22(8): 847–854.
48. Le H.V., Schoenbach V.J., Herrero R., et al. Herpes simplex virus type-2 seropositivity among ever married women in South and North Vietnam: a population-based study. Sex Transm Dis 2009; 36(10): 616–620, http://dx.doi.org/10.1097/OLQ.0b013e3181a8cde4.
49. LeGoff J., Saussereau E., Boulanger M.C., et al. Unexpected high prevalence of herpes simplex virus (HSV) type-2 seropositivity and HSV genital shedding in pregnant women living in an East Paris suburban area. Int J STDAIDS 2007; 18(9): 593–595, http://dx.doi.org/10.1258/095646207781568457.
50. Kasymova E.B., Bashkina O.A., Galimzyanov Kh.M., Netalieva S.Zh. Infectious mononucleosis associated with herpes simplex virus type 4 and 5 in children. Infektsionnye bolezni 2012; 3: 44–47.
51. Emmert D.H. Treatment of common cutaneousherpessimplexvirus infections. Am Fam Physician 2000; 61(6): 1697–1706.
52. Munjoma M.W., Kureva E.N., Mapingure M.P., et al. The prevalence, incidence and risk factors of herpes simplex virus type 2 infection among pregnant Zimbabwean women followed up nine months after childbirth. BMC Women’s Health2010; 10: 2, http://dx.doi.org/10.1186/1472-6874-10-2.
53. Pallier C., Tebourbi L., Chopineau-Proust S., et al. Herpes virus, cytomegalovirus, human sperm and assisted fertilization. Hum Reprod 2002; 17(5): 1281–1287, http://dx.doi.org/10.1093/humrep/17.5.1281.
54. el Borai N., Inoue M., Lefèvre C., et al. Detection of herpes simplex DNA in semen and menstrual blood of individuals attending an infertility clinic. J Obstet Gynaecol Res 1997; 23(1): 17–24.
55. Uchaykin V.F., Smirnov A.V., Chuelov S.B., Rossina A.L. Herpes viral hepatits. Infektsionnye bolezni 2012; 3: 80–82.
56. Wu K.H., Zhou Q.K., Huang J.H., et al. Infection of cytomegalovirus and herpes simplex virus and morphology of infected spermatogenic cells in infertile men. Zhonghua Nan Ke Xue 2007; 13(12): 1075–1079.
57. Yang Y.S., Ho H.N., Chen H.F. Cytomegalovirus infection and viral shedding in genital tract of infertile couples. J Med Virol 1995; 45(2): 179–182.
58. L’vov N.D. Human herpes virus is a systemic, integrative, lymphoproliferative immunooncopathology. Russkij medicinskij zurnal 2012; 20(22): 1133–1137.
59. Gervazieva V.B., Samoylikov P.V. The interaction of Herpesviridae viruses with human immune system. Allergologiya i immunologiya 2010; 11(1): 31–41.
60. Nagasako E.M., Johnson R.W., Griffin D.R., Dworkin R.H. Rash severity inherpes zoster: correlates and relationship to postherpeticneuralgia. J Am Acad Dermatol 2002; 46(6): 834–839.
61. Wrathall A.E., Simmons H.A.,Van Soom A., Simmons A.E. Evaluation of risk of viral transmission to recipients of bovine embryos arising from fertilization with virus-infected semen. Theriogenology 2006; 65(2): 247–274, http://dx.doi.org/10.1016/j.theriogenology.2005.05.043.

Sobchak D.М., Volsky N.Е., Svintsova Т.А., Stchuklina Т.V., Butina Т.Y., Kushman К.V., Korochkina О.V. Human Immune System and Characteristics of Herpetic Infection Pathogenesis (Review). Sovremennye tehnologii v medicine 2014; 6(3): 118