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Reactivation and distribution of bovine herpesvirus 5 DNA in the brain of latently infected sheep

The biology of latent infection by bovine herpesvirus type 5 (BoHV-5) has been studied in cattle and rabbits, yet many aspects remain poorly understood. We herein investigated the suitability of lambs to investigate aspects of BoHV-5 latency. Thirteen six-month-old lambs inoculated intranasally (IN) with BoHV-5 strain SV-507/99 (titer of 10(6.8) TCID50/ mL) shed the virus in nasal secretions in titers up 10(5.5) TCID50/mL, during up to 11 days, developing virus neutralizing (VN) titers of 16 to 128 at day 30 post-inoculation (pi). The inoculated animals developed only a mild serous nasal secretion and transient hyperthermia. Examination of brain sections of five lambs euthanized at day 30 pi by PCR revealed the presence of latent DNA in the trigeminal ganglia (TG, 5 out of five), olfactory bulbs (OB, 5/5), pons (2/5), cerebellum (2/5) and cerebral cortex (1/5). Administration of dexamethasone (Dx, n=4) or flumethasone (FluM, n=4) to eight latently infected lambs at day 65 pi resulted in virus reactivation and shedding by 3 out of 4 individuals in each group. Virus shedding in nasal secretions started at day 3 post-treatment and lasted up to five days (1-5) in Dx treated lambs (titers up to 10(2.8)TCID50/mL), was delayed and lasted up to three days (1-3) in FluM-treated lambs (titers up to 10(2.1) TCID50/mL). PCR examination of the brains of animals submitted to reactivation, at day 30 post-treatment, showed a pattern of distribution of latent viral DNA fairly similar to that found in those not submitted to reactivation. In summary, the ability of BoHV-5 to establish latent infection, the consistent colonization of TGs and OBs by latent viral DNA and virus reactivation induced by corticosteroid treatment are promising findings towards the use of lambs to study selected aspects of BoHV-5 latency.

BoHV-5; latency; lambs; animal model; corticoids


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