ABSTRACT
Latent infection with bovine herpesvirus type-5 (BHV-5) was established in rabbits inoculated with two South American isolates (EVI-88 and 613) by intranasal or conjunctival routes. Nine rabbits (613, 8/27; EVI-88, 1/34) developed neurological disease and died during acute infection and other three (613, n=2; EVI-88, n=1) developed a delayed neurological disease, at days 34, 41 and 56 post-inoculation (p.i.). Between days 56 and 62 p.i., the remaining rabbits were submitted to five daily administrations of dexamethasone (Dx) to reactivate the infection. Twenty-five out of 44 rabbits (56.8%) shed virus in nasal or ocular secretions after Dx treatment. Virus shedding was first detected at day two post-Dx and lasted from one to 11 days. The highest frequencies of virus reactivation were observed in rabbits inoculated conjunctivally (10/15 versus 15/29); and among rabbits infected with isolate 613 (12/16 versus 13/28). Virus reactivation upon Dx treatment was accompanied by neurological disease in nine rabbits (20.4%), resulting in six deaths (13.6%). Virus in moderate titers and mild to moderate non-suppurative inflammatory changes in the brain characterized the neurological infection. Three other rabbits showed severe neurological signs followed by death after 31 to 54 days of Dx treatment. Virus, viral nucleic acids and inflammatory changes were detected in their brains. The late-onset neurological disease, after acute infection or Dx treatment, was probably a consequence of spontaneous virus reactivation. These results demonstrate that BHV-5 does establish a latent infection in rabbits and that clinical recrudescence may occur upon reactivation.
Subject(s)
Encephalitis, Viral/veterinary , Herpesviridae Infections/veterinary , Herpesvirus 5, Bovine/physiology , Meningoencephalitis/veterinary , Acute Disease , Administration, Intranasal , Animals , Cattle , Cattle Diseases/virology , Cell Line , Cerebral Cortex/virology , Dexamethasone/administration & dosage , Dexamethasone/pharmacology , Disease Models, Animal , Encephalitis, Viral/virology , Herpesviridae Infections/virology , Herpesvirus 5, Bovine/drug effects , Herpesvirus 5, Bovine/pathogenicity , Meningoencephalitis/virology , Rabbits , Virus Activation/drug effects , Virus Latency , Virus Replication , Virus SheddingABSTRACT
The reproduction effects of bovine viral diarrhea virus type-2 (BVDV-2) infection were investigated in ewes inoculated with a non-cytopathic BVDV-2 isolate at three stages of gestation. Virus inoculation was followed by a transient viremia, accompanied by a transient and mild hyperthermia and nasal discharge in a few animals. Some ewes were sacrificed at different time-points after virus inoculation to study the kinetics of fetal infection. Infectivity and viral antigens were detected in placentomes from day 7 to 36 post-inoculation (pi) and in fetal fluids and tissues between days 10 and 28 pi. Cardiac petechial hemorrhages and hemoperitoneum accompanied by a severe fibrinous ulcerative placentitis were observed in fetuses examined at days 21, 28 and 36 pi. Inoculation of ewes at days 55-60 of gestation resulted in a prolonged virus replication in placentomes and fetal tissues; ewes that were allowed to proceed with pregnancy had 77% of abortions or fetal and perinatal deaths. Seven stillbirths, unviable and viable lambs born to these ewes were virus-positive at birth. Infectious virus was repeatedly isolated from leukocytes of two lambs up to 2 and 6 months of age, indicating they were persistently infected. Ewes inoculated at days 65-70 of gestation had 66.6% of fetal and perinatal losses. Three viable lambs born to these ewes were healthy, BVDV antibody-positive and virus-negative. A transient viral replication in placentomes and in a few fetal tissues, followed by the rise of fetal neutralizing antibodies and virus clearance was the result of inoculating ewes at days 120-125 of gestation. Lambs born to these ewes were healthy, antibody-positive and virus-negative. These results demonstrate that the biology of BVDV-2 infection in pregnant sheep is essentially similar to that of BVDV-1 in pregnant cattle and sheep. These features make this species an attractive animal model for studying the pathogenesis of congenital BVDV-2 infection.