Skip to main content
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2007 Nov 6;17(12):1196–1209. doi: 10.1016/S0046-8177(86)80561-5

Intrauterine latent herpes simplex virus infectiona

I. Spontaneous abortion

James A Robb 1,*, Kurt Benirschke , Robert Barmeyer
PMCID: PMC7131424  PMID: 3025072

Abstract

Herpes simplex virus (HSV, probably type 2) antigen was detected in nonpregnant and pregnant endometria, placentae, umbilical cords, and neonatal tissues (companion paper) by avidinbiotin complex immunohistochemical studies. HSV cytologic abnormalities were not detected in any of the 380 cases examined: included were specimens from therapeutic and spontaneous abortions (200 cases) and endometrial curettage (180 cases). The presence of inflammation was not correlated with HSV positivity. Endometrial HSV positivity was significantly correlated with normal late secretory phase (40 per cent of specimens positive), abnormal secretory phase (67 per cent positive), and therapeutic (33 per cent positive) versus spontaneous (26 per cent positive) abortions. Placental HSV positivity was significantly correlated with spontaneous (39 per cent positive) versus therapeutic (14 per cent positive) abortions and with blighted ova (67 per cent positive). No significant correlation was found between HSV positivity and a clinical history of oral or genital HSV infection in either the patient or the male partner. The data support the concept of a subclinical latent intrauterine endometrial HSV infection that is hormonally regulated and can produce transplacental infection of the embryo or fetus, with variable consequences.

Footnotes

a

Presented in part in poster format at the 1984 International Academy of Pathology annual meeting (Lab Invest 50:50A, 1984). Supported by Scripps Clinic General Research Center Clinfo Computer-NIH Division of Research Resources grant RR-00833 for data analysis and institutional overhead for facilities.

References

  • 1.Nahmias AJ, Keyserling HL, Kerrick GM. Herpes simplex. In: Remington JS, Klein JO, editors. Infectious Diseases of the Fetus and Newborn Infant. ed 2. WB Saunders; Philadelphia: 1983. pp. 636–678. [Google Scholar]
  • 2.Sullivan-Bolyai J, Hull HF, Wilson C. Neonatal herpes simplex virus infection in King County, Washington. JAMA. 1983;250:3059. [PubMed] [Google Scholar]
  • 3.Robb JA. A new enzyme immunolectin tissue stain. Diagn Med. 1981;4:87. [Google Scholar]
  • 4.Robb JA, Benirschke K, Mannino F. Intrauterine latent herpes simplex virus infection. II. Latent neonatal infection. Hum Pathol. 1986;17:000. doi: 10.1016/s0046-8177(86)80562-7. [DOI] [PubMed] [Google Scholar]
  • 5.Goldman RL. Herpetic inclusions in the endometrium. Obstet Gynecol. 1970;36:603. [PubMed] [Google Scholar]
  • 6.Abraham AA. Herpesvirus hominis endometritis in a young woman wearing an intrauterine contraceptive device. Am J Obstet Gynecol. 1978;3:340. doi: 10.1016/0002-9378(78)90611-7. [DOI] [PubMed] [Google Scholar]
  • 7.Mazur MT, Hendrickson MR, Kempson RL. Optically clear nuclei, an alteration of endometrial epithelium in the presence of trophoblast. Am J Surg Pathol. 1983;7:415. [PubMed] [Google Scholar]
  • 8.Cohen C, Trapuckd S. Leukocytoclastic vasculitis associated with cutaneous infection by herpesvirus. Am J Dermatopathol. 1984;6:561. doi: 10.1097/00000372-198412000-00008. [DOI] [PubMed] [Google Scholar]
  • 9.Macarak EJ, Friedman HM, Kefalides NA. Herpes simplex virus type 1 infection of endothelium reduces collagen and fibronectin synthesis. Lab Invest. 1985;53:280. [PubMed] [Google Scholar]
  • 10.Melnick JL, Dreesman GR, McCollum CH. Cytomegalovirus antigen within human arterial smooth muscle cells. Lancet. 1983;2:644. doi: 10.1016/s0140-6736(83)92529-1. [DOI] [PubMed] [Google Scholar]
  • 11.Myerson D, Hackman RC, Nelson JA. Widespread presence of histologically occult cytomegalovirus. Hum Pathol. 1984;15:430. doi: 10.1016/s0046-8177(84)80076-3. [DOI] [PubMed] [Google Scholar]
  • 12.Gilman SC, Docherty JJ, Rawls WE. Antibody response in humans to individual proteins of herpes simplex viruses. Infect Immun. 1981;34:880. doi: 10.1128/iai.34.3.880-887.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Robb JA, Bond CW, Leibowiz JL. Pathogenic murine coronaviruses III. Biological and biochemical characterization of temperature-sensitive mutants of JHMV. Virology. 1979;94:385. doi: 10.1016/0042-6822(79)90469-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Redfield DC, Richman DD, Albanil S. Detection of herpes simplex virus in clinical specimens by DNA hybridization. Diagn Microbil Infect Dis. 1983;1:117. doi: 10.1016/0732-8893(83)90041-x. [DOI] [PubMed] [Google Scholar]
  • 15.Stroop WG, Rock DL, Fraser NW. Localization of herpes simplex virus in the trigeminal and olfactory systems of the mouse central nervous system during acute and latent infections by in situ hybridization. Lab Invest. 1984;51:27. [PubMed] [Google Scholar]
  • 16.Rapp F. Alan R. Liss; New York: 1984. Herpesvirus. [Google Scholar]
  • 17.Roizman B, Batterson W. Herpesviruses and their replication. In: Fields BN, editor. Virology. Raven Press; New York: 1985. pp. 497–526. [Google Scholar]
  • 18.Dako Labs rabbit anti-HSV 1 and 2 IgG package insert. November 1975 (5 references listed in insert from the Scandinavian literature)
  • 19.Showalter SD, Zweig M, Hampar B. Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP4. Infect Immun. 1981;34:684. doi: 10.1128/iai.34.3.684-692.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Pereira L, Dondero DV, Gallo D. Serological analysis of herpes simplex virus types 1 and 2 with monoclonal antibodies. Infect Immun. 1982;35:363. doi: 10.1128/iai.35.1.363-367.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Rawls WE, Balachandran N, Sisson G. Localization of a type-specific antigenic site on herpes simplex virus type 2 glycoprotein D. J Virol. 1984;51:263. doi: 10.1128/jvi.51.1.263-265.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Dowbenko DJ, Lasky LA. Extensive homology between the herpes simplex virus type 2 glycoprotein F gene and the herpes simplex virus type 1 glycoprotein C gene. J Virol. 1984;52:154. doi: 10.1128/jvi.52.1.154-163.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Zweig M, Showalter SD, Simms DJ. Antibodies to a synthetic oligopeptide that react with herpes simplex virus type 1 and 2 glycoprotein C. J Virol. 1984;51:430. doi: 10.1128/jvi.51.2.430-436.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Holland TC, Marlin SD, Levine M. Antigenic variants of herpes simplex virus selected with glycoprotein specific monoclonal antibodies. J Virol. 1983;45:672. doi: 10.1128/jvi.45.2.672-682.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Pickles VR, Hall WJ, Best FA. Prostaglandins in endometrium and menstrual fluid from normal and dysmenorrhoeic subjects. J Obstet Gynaecol Br Commonw. 1965;72:185. doi: 10.1111/j.1471-0528.1965.tb01415.x. [DOI] [PubMed] [Google Scholar]
  • 26.Goodwin JS, Webb DR. Regulation of the immune response by prostaglandins, a review. Clin Immunol Immunopathol. 1980;15:106. doi: 10.1016/0090-1229(80)90024-0. [DOI] [PubMed] [Google Scholar]
  • 27.Rawls WE. Herpes simplex virus. In: Fields BN, editor. Virology. Raven Press; New York: 1985. pp. 527–561. [Google Scholar]
  • 28.Blyth WA, Hill TJ, Field HJ. Reactivation of herpes simplex virus infection by ultraviolet light and possible involvement of prostaglandins. J Gen Virol. 1976;33:547. doi: 10.1099/0022-1317-33-3-547. [DOI] [PubMed] [Google Scholar]
  • 29.Baker DA, Thomas J, Epstein J. The effect of prostaglandins on the multiplication and cell-to-cell spread of herpes simplex virus type 2 in vitro. Am J Obstet Gynecol. 1982;144:346. doi: 10.1016/0002-9378(82)90589-0. [DOI] [PubMed] [Google Scholar]
  • 30.Terragno NA, Terragno DA, Packolczyk D. Prostaglandins and the regulation of uterine blood flow in pregnancy. Nature. 1974;249:57. doi: 10.1038/249057a0. [DOI] [PubMed] [Google Scholar]
  • 31.Brown ZA, Vontver LA, Benedetti J. Genital herpes in pregnancy: risk factors associated with recurrences and asymptomatic viral shedding. Am J Obstet Gynecol. 1985;153:24. doi: 10.1016/0002-9378(85)90584-8. [DOI] [PubMed] [Google Scholar]
  • 32.Cabral GA, Marciano-Cabral F, Fry D. Expression of herpes simplex virus type 2 antigens in premalignant and malignant human vulvar cells. Am J Obstet Gynecol. 1982;143:611. doi: 10.1016/0002-9378(82)90105-3. [DOI] [PubMed] [Google Scholar]
  • 33.Persson RH, Bacchetti S, Smiley JR. Cells that constitutively express the herpes simplex virus immediate-early protein ICP4 allow efficient activation of viral delayed-early genes in trans. J Virol. 1985;54:414. doi: 10.1128/jvi.54.2.414-421.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Bradley JS, Yeager AS, Dyson DC. Neutralization of herpes simplex virus by antibody in amniotic fluid. Obstet Gynecol. 1982;60:318. [PubMed] [Google Scholar]
  • 35.Kumar A, Madden DL, Nankervis GA. Humoral and cell-mediated responses to herpesvirus antigens during pregnancy-a longitudinal study. J Clin Immunol. 1984;4:12. doi: 10.1007/BF00915281. [DOI] [PubMed] [Google Scholar]
  • 36.Redline RW, Abramowsky CR. Clinical and pathologic aspects of recurrent placental villitis. Hum Pathol. 1985;16:727. doi: 10.1016/s0046-8177(85)80159-3. [DOI] [PubMed] [Google Scholar]
  • 37.Clewell WH, Manchester DK. Recurrent maternal floor infarction: a preventable cause of fetal death. Am J Obstet Gynecol. 1983;147:346. doi: 10.1016/0002-9378(83)91130-4. [DOI] [PubMed] [Google Scholar]
  • 38.Naeye RL. Maternal floor infarction. Hum Pathol. 1985;16:823. doi: 10.1016/s0046-8177(85)80254-9. [DOI] [PubMed] [Google Scholar]
  • 39.Pickles VR. The menstrual stimulant in puberty. J Physiol (Lond) 1966;183:69. [Google Scholar]
  • 40.Garcia A. Maternal herpes-simplex infection causing abortion: histopathologic study of the placenta. O Hospital. 1970;78:1266. [PubMed] [Google Scholar]
  • 41.Nahmias AJ, Josey WE, Naib ZM. Perinatal risk associated with maternal genital herpes simplex virus infection. Am J Obstet Gynecol. 1971;110:825. doi: 10.1016/0002-9378(71)90580-1. [DOI] [PubMed] [Google Scholar]
  • 42.Blaustein A. ed 2. Springer-Verlag; New York: 1982. p. 139. (Pathology of the Female Genital Tract). [Google Scholar]
  • 43.Nahmias AJ, Keyserling HL, Kerrick GM. Herpes simplex. In: Remington JS, Klein JO, editors. Infectious Diseases of the Fetus and Newborn Infant. WB Saunders; Philadelphia: 1983. p. 641. [Google Scholar]
  • 44.Griffith BP, McCormick SR, Fong CKY. The placenta as a site of cytomegalovirus infection in guinea pigs. J Virol. 1985;55:402. doi: 10.1128/jvi.55.2.402-409.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Visintine A, Nahmias A. Neonatal herpes simplex virus infection of the central nervous system. Proceedings of the 4th International Congress of Virology; The Hague, The Netherlands; 1978. [Google Scholar]
  • 46.Corey L, Adams HG, Brown ZA. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med. 1983;98:958. doi: 10.7326/0003-4819-98-6-958. [DOI] [PubMed] [Google Scholar]
  • 47.Bolognese RJ, Corson SL, Fuccillo DA. Herpesvirus hominis type II infections in asymptomatic pregnant women. Obstet Gynecol. 1976;48:507. [PubMed] [Google Scholar]
  • 48.Stagno S, Whitley RJ. Herpesvirus infections of pregnancy. N. Engl J Med. 1985;313(part I):1270. doi: 10.1056/NEJM198511143132006. [DOI] [PubMed] [Google Scholar]; Stagno S, Whitley RJ. Herpesvirus infections of pregnancy. N Engl J Med. 1985;313(part II):1327. doi: 10.1056/NEJM198511213132105. [DOI] [PubMed] [Google Scholar]
  • 49.Cleveland PH, Richmond DD, Redfield DC. Enzyme immunofitration technique for rapid diagnosis of herpes simplex virus eye infections in a rabbit model. J Clin Microbiol. 1982;16:676. doi: 10.1128/jcm.16.4.676-685.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Zheng ZM, Hsiung GD. Complement-requiring neutralizing antibody in guinea pigs with primary and recurrent genital herpes. Proc Soc Exp Biol Med. 1984;177:332. doi: 10.3181/00379727-177-41952. [DOI] [PubMed] [Google Scholar]
  • 51.Chow TC, Hsiung GD. Neonatal herpes simplex virus infection in guinea pigs. Proc Soc Exp Biol Med. 1982;170:459. doi: 10.3181/00379727-170-41459. [DOI] [PubMed] [Google Scholar]

Articles from Human Pathology are provided here courtesy of Elsevier

RESOURCES