Abstract
Bovine herpesvirus type 5 (BHV-5) is a major agent of meningoencephalitis in cattle and establishes latent infections mainly in sensory nerve ganglia. The distribution of latent BHV-5 DNA in the brain of rabbits prior to and after virus reactivation was studied using a nested PCR. Fifteen rabbits inoculated intranasally with BHV-5 were euthanized 60 days post-inoculation (group A, N = 8) or submitted to dexamethasone treatment (2.6 mg kg(-1) day(-1), im, for 5 days) and euthanized 60 days later (group B, N = 7) for tissue examination. Two groups of BHV-1-infected rabbits (C, N = 3 and D, N = 3) submitted to each treatment were used as controls. Viral DNA of group A rabbits was consistently detected in trigeminal ganglia (8/8), frequently in cerebellum (5/8), anterior cerebral cortex and pons-medulla (3/8) and occasionally in dorsolateral (2/8), ventrolateral and posterior cerebral cortices, midbrain and thalamus (1/8). Viral DNA of group B rabbits showed a broader distribution, being detected at higher frequency in ventrolateral (6/7) and posterior cerebral cortices (5/7), pons-medulla (6/7), thalamus (4/7), and midbrain (3/7). In contrast, rabbits inoculated with BHV-1 harbored viral DNA almost completely restricted to trigeminal ganglia and the distribution did not change post-reactivation. These results demonstrate that latency by BHV-5 is established in several areas of the rabbit's brain and that virus reactivation leads to a broader distribution of latent viral DNA. Spread of virus from trigeminal ganglia and other areas of the brain likely contributes to this dissemination and may contribute to the recrudescence of neurological disease frequently observed upon BHV-5 reactivation.
Highlights
The establishment of latent infection in neurons of sensory and autonomic nerve ganglia is the hallmark of infection by human and animal α-herpesviruses and has profound implications in the epidemiology and pathogenesis of these conditions [1]
The present results confirm and extend our findings in rabbits in which Bovine herpesvirus type 5 (BHV-5) DNA was detected in several different areas of the brain of experimentally infected calves [25]
BHV-5 DNA was detected in several areas of the brain of latently infected rabbits prior to Dx-induced reactivation
Summary
The establishment of latent infection in neurons of sensory and autonomic nerve ganglia is the hallmark of infection by human and animal α-herpesviruses and has profound implications in the epidemiology and pathogenesis of these conditions [1]. Recrudescence of clinical disease (orolabial, nasal and genital lesions, encephalitis) is a well-documented consequence of reactivation of human and some animal herpesviruses [3,4,5]. In animals surviving acute infection, BHV-5 establishes a lifelong latent infection that can be reactivated under certain natural or induced stimuli [4,5]. In contrast to many other animal herpes virus infections, BHV-5 reactivation is frequently accompanied by recrudescence of clinical disease, both in the natural host and in a rabbit model [4,5]
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