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Journal of Virology, March 2006, p. 2823-2831, Vol. 80, No. 6
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.6.2823-2831.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Carlos Ramirez,
Fernando Guzman-Sanchez,
Juan M. Alfaro,
Isabel Sastre, and
Fernando Valdivieso*
Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Madrid, Spain
Received 22 September 2005/ Accepted 22 December 2005
Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that causes severe disease and death in newborn humans but, to date, it remains unclear how neonatal infection occurs. We show here that the vertical transmission of HSV-1 in mice is mainly hematogenous and involves the colonization of the neonate central nervous system (CNS). HSV-1 DNA was mainly detected in the blood and CNS of the offspring born to latently infected mothers; no significant differences were seen between the viral DNA concentrations in the blood of these mothers and their female progeny (either neonate or adult). The administration of acyclovir during gestation reduced or eliminated both the maternal and the neonatal viral DNA in the blood. Embryo transfer was performed to ensure (as far as possible) that only vertical hematogenous infection took place. Immunohistochemical analysis detected viral proteins in the encephalon of the offspring. Immunofluorescence studies provided immunoreactive evidence of HSV-1 proteins in the neurons of the hippocampus and showed that these viruses can molecularly reactivate after hyperthermia. Neonatal HSV-1 infection therefore appears to be mainly caused by hematogenous vertical transmission, and the viruses that colonize the offspring CNS are capable of molecular reactivation after a period of latency.
J.S.B. and C.R. contributed equally to this study.
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