Abstract
Disseminated herpes simplex virus type 1 (HSV-1) infection during pregnancy is poorly described even though it is associated with high maternal and fetal morbidity and neonatal mortality in humans. In a previous paper using mice as a model, the authors demonstrated that HSV-1 is transmitted hematogenously from mother to offspring, the virus colonizing the central nervous system and provoking high mortality. In the present study, viral DNA levels in latently infected mothers were investigated during pregnancy and after delivery in mice. Samples from different organs were obtained before gestation (latency), three times during pregnancy (17, 4.5, and 1 day before delivery), and four times after delivery (1 day, 1 week, 1 and 2 months). A dramatic decrease in viral DNA concentration was observed during pregnancy, especially in the nervous system, with postnatal recovery to latent levels. All the brain regions studied showed similar trends. The viral copy numbers detected in mothers at delivery +1 day were independent of viral inoculum size. The spread of the virus to the above organs was examined immunohistochemically and, in general, more intense viral staining was observed after delivery in each. Because immunoglobulin levels can be modified by infections during pregnancy, the authors examined the levels of specific HSV-1 antibodies. Variation in HSV-1 DNA concentration was found to be associated with changes in the full spectrum of immunoglobulins (but especially immunoglobulin M [IgM]) over pregnancy, whereas at delivery −1 day a significant inverse relationship between immunoglobulins and HSV-1 DNA was observed. IgGs provided protection during the postnatal phase.
This work was supported by a grant from the Obra Social Caja Madrid to the Asociación de Familiares de Enfermos de Alzheimer (AFAL), and by an institutional grant by the Fundación Areces to the Centro de Biología Molecular Severo Ochoa. The authors thank Prof. F. Mayor for continuous encouragement and help, and Dr. L. Carrasco for providing the HSV-1 KOS strain. The authors are grateful to J. Ripoll for excellent technical assistance.