Placenta in chronic herpesvirus infection: morphological changes and perinatal outcomes
https://doi.org/10.36604/1998-5029-2025-97-152-159
Abstract
High prevalence of herpes-virus infection among women of reproductive age and the possibility of latent persistence with subsequent reactivation highlight the importance of studying the morphological changes in the placenta that arise when infected with herpes simplex viruses (HSV) types 1 and 2. This article provides a morphological characterisation of placental alterations in herpesvirus infection and their association with the development of perinatal pathology in the fetus. Microscopic features that allow suspicion of herpetic placental involvement are described: chronic villitis, intervillositis, vasculitis, focal villous necrosis, trophoblast destruction, damage to Kachchenko–Hofbauer cells, and formation of giant multinucleated cells with viral inclusions (Cowdry type B HSV cells). Differences between HSV-1 and HSV-2 are analysed with respect to the severity of inflammatory-destructive and vascular changes, as well as the clinical consequences of intra-uterine infection. A greater neurotropism and propensity for generalised infection of HSV-2 compared with HSV-1 is noted. The review was prepared using publications indexed in international and Russian scientific databases, including PubMed, eLibrary and Google Scholar. Search terms included: herpetic placentitis, intervillositis, funiculitis, placental pathomorphology, fetoplacental insufficiency, association with perinatal pathology and their combinations in Russian and English.
About the Author
T. S. Churikova
Far Eastern Scientific Center of Physiology and Pathology of Respiration; Amur State Medical Academy
Russian Federation
Russian Federation
Tatyana S. Churikova, Junior Staff Scientist, Laboratory of Mechanisms of Etiopathogenesis and Recovery Processes of the Respiratory System at Non-Specific Lung Diseases; Postgraduate Student, Department of Pathology with a Course in Forensic Medicine
22, Kalinina Str., Blagoveshchensk, 675000
95 Gor'kogo Str., Blagoveshchensk
References
1. Felker A.M., Nguyen P., Kaushic C. Primary HSV2 infection in early pregnancy results in transplacental viral transmission and dose-dependent adverse pregnancy outcomes in a novel mouse model. Viruses 2021; 13(10):1929. https://doi.org/10.3390/v13101929
2. Andrievskaya I.A., Zhukovets I.V., Dovzhikova I.V., Ishutina N.A., Petrova K.K. The effect of HSV-1 seropositivity on the course of pregnancy, childbirth and the condition of newborns. Microorganisms 2022; 10(1):176. https://doi.org/10.3390/microorganisms10010176
3. Looker K.J., Magaret A.S., May M.T., Turner K.M., Vickerman P., Newman L.M., Gottlieb S.L. Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012. PLoS One 2015; 10(10):e0140765. https://doi.org/10.1371/journal.pone.0140765
4. Xu F., Markowitz L.E., Gottlieb S.L., Berman S.M. Seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the United States. Am. J. Obstet. Gynecol. 2007; 196(1):43.e1–43.e6. https://doi.org/10.1016/j.ajog.2006.07.051
5. Finger-Jardim F., Avila E.C., da Hora V.P., Gonçalves C.V., de Martinez A.M.B., Soares M.A. Prevalence of herpes simplex virus types 1 and 2 at maternal and fetal sides of the placenta in asymptomatic pregnant women. Am. J. Reprod. Immunol. 2017; 78(1):e12689. https://doi.org/10.1111/aji.12689
6. Deftereou T.E., Trypidi A., Alexiadi C.A., Theotokis P., Manthou M.E., Meditskou S., Simopoulou M., Lambropoulou M. Congenital herpes simplex virus: a histopathological view of the placenta. Cureus 2022; 14(9):e29101. https://doi.org/10.7759/cureus.29101
7. Smith A.E., McKenney A., Rabinowitz L., Das A. Diagnosis of neonatal herpes simplex infection from the placenta. Case Rep. Pediatr. 2020; 2020:8898612. https://doi.org/10.1155/2020/8898612
8. Milovanov A.P. [Pathology of the mother-placenta-fetus system: a guide for physicians]. Moscow: Meditsina; 1999 (in Russian). ISBN: 5-225-02775-Х.
9. Pshukova E.M. [Morphology of placenta changes in intrauterine infections]. Meditsina. Sotsiologiya. Filosofiya. Prikladnyye issledovaniya 2022; 1:3–6 (in Russian).
10. Nadeev A.P., Shkurupiy V.A., Marinkin I.O. [Liver and placenta in peri- and postnatal periods in pathology]. Novosibirsk: Nauka; 2014 (in Russian).
11. Finger-Jardim F., Teixeira L.O., Rodrigues de Oliveira G., Martínez Barral M.F., da Hora V.P., Gonçalves C.V., Soares M.A., de Martinez A.M.B. Herpes simplex virus: prevalence in placental tissue and incidence in neonatal cord blood samples. J. Med. Virol. 2014; 86(3):519–524. https://doi.org/10.1002/jmv.23817
12. Nadeev A.P., Travin M.P., Drobinskaya A.N. [Features of placental infection with cytomegalovirus and herpes simplex virus type 2 in term pregnancy]. Journal of Siberian Medical Sciences 2015; 3:83.
13. Fakonti G., Pantazi P., Bokun V., Holder B. Placental macrophage (Hofbauer cell) responses to infection during pregnancy: a systematic scoping review. Front. Immunol. 2022; 12:756035. https://doi.org/10.3389/fimmu.2021.756035
14. Melnikova V.F. [Pathological anatomy of placental lesions caused by viruses (respiratory and herpes simplex) and mycoplasmas: abstract of Doctor’s degree dissertation thesis]. St. Petersburg; 1992 (in Russian).
15. Fedotova Ye.P., Tsinzerling A.V., Mel'nikova V.F., Popova Ye.D. [The placenta in herpes infection]. Arkhiv Patologii = Archive of Pathology 1984; 46(10):51–57 (in Russian).
16. Nizyaeva N.V. [Histological criteria of inflammatory changes in the placental villous tree]. Mezhdunarodnyy zhurnal prikladnykh i fundamental′nykh issledovaniy 2018; 2:202–207 (in Russian).
17. Karimova F.D., Radzhabova Z.A. [Experience of studying the development of fetoplacental insufficiency in herpesvirus infection]. Vrach-aspirant 2012; 1(50):76–83 (in Russian).
18. Nasyrov R.A., Sidorova N.A., Melnikova V.F., Fedotova E.P. Morphological and immunohistochemical features of placental damage in cases of perinatal death: institutional experience with emphasis on viral etiology. Ann. Clin. Lab. Sci. 2020; 50(6):754–760.
19. Heerema-McKenney A. Diagnostic pathology: placenta. Elsevier Science; 2018. ISBN: 9780323609715.
20. Edwards M.S., Popek E.J., Wise B., Hatzenbuehler L., Arunachalam A.R., Hair A.B. Ascending in utero herpes simplex virus infection in an initially healthy-appearing premature infant. Pediatr. Dev. Pathol. 2015; 18(2):155–158. https://doi.org/10.2350/14-09-1548-CR.1
21. Marsh B., Zhou Y., Kapidzic M., Fisher S., Blelloch R. Regionally distinct trophoblast regulate barrier function and invasion in the human placenta. Elife 2022; 11:e78829. https://doi.org/10.7554/eLife.78829
22. Koi H., Zhang J., Makrigiannakis A., Getsios S., MacCalman C.D., Strauss J.F.3rd, Parry S. Syncytiotrophoblast is a barrier to maternal fetal transmission of herpes simplex virus. Biol. Reprod. 2002; 67(5):1572–1579. https://doi.org/10.1095/biolreprod.102.004325
23. Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W., Lambris J.D., Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. J. Virol. 1998; 72(9):7064–7074. https://doi.org/10.1128/JVI.72.9.7064-7074.1998
24. Bendon R.W., Perez F., Ray M.B. Herpes simplex virus: fetal and decidual infection. Pediatr. Pathol. 1987; 7(1):63–70. https://doi.org/10.1080/15513818709177115
25. Redline R.W. Distal villous immaturity. Diagn. Histopathol. 2012; 18(5):189–194. https://doi.org/10.1016/j.mpdhp.2012.02.002
26. Heifetz S.A., Bauman M. Necrotizing funisitis and herpes simplex infection of placental and decidual tissues: study of four cases. Hum. Pathol. 1994; 25(7):715–722. https://doi.org/10.1016/0046-8177(94)90306-9
27. Herpes simplex. In: Kimberlin D.W., Barnett E.D., Lynfield R., Sawyer M.H., eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics; 2021:407–417.
28. Corey L., Whitley R.J., Stone E.F., Mohan K. Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome. Lancet 1988; 1(8575-6):1–4. https://doi.org/10.1016/S0140-6736(88)90997-X
29. Marquez L., Levy M.L., Munoz F.M., Palazzi D.L. A report of three cases and review of intrauterine herpes simplex virus infection. Pediatr. Infect. Dis. J. 2011; 30(2):153–157. https://doi.org/10.1097/INF.0b013e3181f55a5c
30. Lopushinsky K.M., Harabor A., Bodani J. No footprint too small: case of intrauterine herpes simplex virus infection. Case Rep. Perinat. Med. 2021; 10(1):20210047. https://doi.org/10.1515/crpm-2021-0047
31. El-Atawi K.M., Elhalik M.S., Farid A.R. Congenital herpes simplex type-2 infection; challenges and solutions. J. Clin. Neonatol. 2016; 5(3):205–208. https://doi.org/10.4103/2249-4847.191269
32. Toth C., Harder S., Yager J. Neonatal herpes encephalitis: a case series and review of clinical presentation. Can. J. Neurol. Sci. 2003; 30(1):36–40. https://doi.org/10.1017/S0317167100002419
33. El Azazi M., Malm G., Forsgren M. Late ophthalmologic manifestations of neonatal herpes simplex virus infection. Am. J. Ophthalmol. 1990; 109(1):1–7. https://doi.org/10.1016/S0002-9394(14)75569-2
34. Hammad W.A.B., Konje J.C. Herpes simplex virus infection in pregnancy-an update. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021; 259:38–45. https://doi.org/10.1016/j.ejogrb.2021.01.055
35. Oliveira Í., Fernandes A., Pereira M.J., Capela J., Calado C. Intrauterine herpes simplex virus infection: insights into a silent threat. Cureus 2025; 17(1):e78173. https://doi.org/10.7759/cureus.78173
36. De Rose D.U., Bompard S., Maddaloni C., Bersani I., Martini L., Santisi A., Longo D., Ronchetti M.P., Dotta A., Auriti C. Neonatal herpes simplex virus infection: from the maternal infection to the child outcome. J. Med. Virol. 2023; 95(8):e29024. https://doi.org/10.1002/jmv.29024
37. Avgil M., Ornoy A. Herpes simplex virus and Epstein–Barr virus infections in pregnancy: consequences of neonatal or intrauterine infection. Reprod. Toxicol. 2006; 21(4):436–445. https://doi.org/10.1016/j.reprotox.2004.11.014
Review
For citations:
Churikova T.S. Placenta in chronic herpesvirus infection: morphological changes and perinatal outcomes. Bulletin Physiology and Pathology of Respiration. 2025;(97):152-159. (In Russ.) https://doi.org/10.36604/1998-5029-2025-97-152-159
Views:
169
JATS XML
Email this article 