Borna disease virus 1 infection in alpacas: Comparison of pathological lesions and viral distribution to other dead-end hosts

Abstract

Borna disease is a progressive meningoencephalitis caused by spillover of the Borna disease virus 1 (BoDV-1) to horses and sheep and has gained attention due to its zoonotic potential. New World camelids are also highly susceptible to the disease; however, a comprehensive description of the pathological lesions and viral distribution is lacking for these hosts. Here, the authors describe the distribution and severity of inflammatory lesions in alpacas ( n = 6) naturally affected by this disease in comparison to horses ( n = 8) as known spillover hosts. In addition, the tissue and cellular distribution of the BoDV-1 was determined via immunohistochemistry and immunofluorescence. A predominant lymphocytic meningoencephalitis was diagnosed in all animals with differences regarding the severity of lesions. Alpacas and horses with a shorter disease duration showed more prominent lesions in the cerebrum and at the transition of the nervous to the glandular part of the pituitary gland, as compared to animals with longer disease progression. In both species, viral antigen was almost exclusively restricted to cells of the central and peripheral nervous systems, with the notable exception of virus-infected glandular cells of the Pars intermedia of the pituitary gland. Alpacas likely represent dead-end hosts similar to horses and other spillover hosts of BoDV-1.

Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection

“…In regions where the virus has only recently entered, the strong lymphocytic reaction might still be lacking in contrast to regions which have been infected longer. In contrast to reports in animals, where a circumscribed virus presence has been shown [ 32 , 33 ], there is a broad virus distribution covering almost every region of the human brain. An obvious explanation for this constellation could be the significantly longer survival time of human patients due to intensive care and immunosuppressive treatment.…”

Lethal Borna disease virus 1 (BoDV-1) infections of humans and animals – in-depth molecular epidemiology and phylogeography

“…Many cases in this study were diagnosed only by retrospective analysis of encephalitis cases and it is likely that particularly in the past a considerable proportion of fatal BoDV-1 infections remained undetected 7 . This proportion may have been comparably higher for possible non-fatal infections due to a lower alertness of physicians to such cases and to the limited availability of diagnostic material for direct intra vitam detection of BoDV-1 , which is hampered by the remarkable restriction of BoDV-1 to the central nervous system in erroneous spillover hosts 1,7,9,20,24,34,71 . However, the estimated prevalence of bornavirus-reactive antibodies did not exceed 0.24% in recent serological surveys of healthy individuals or neuropsychiatric patients in known endemic areas 65,67,72 .…”

“…The exact source and route of transmission remain elusive for almost all BoDV-1 infections in humans and domestic mammals. Due to its almost exclusively neurotropic nature in non-reservoir hosts 7,9,20,24,71 , transmission chains between spill-over hosts can be virtually excluded, with the exception of a so far singular iatrogenic transmission event by solid organ transplantation 8 . This leaves infected shrews as the most likely infection source.…”

“…In domestic mammals and humans, BoDV-1 establishes a persistent and strictly neurotropic infection mainly of the central nervous system, with so far no evidence of shedding of infectious virus. The infection usually results in non-purulent encephalomyelitis due to T lymphocytemediated immunopathology with a high case fatality rate 1,7,9,19,20 . The incubation period is presumably highly variable and assumed to range from several weeks to a few months in most cases 8,21,22 .…”