Infection of the enteric nervous system by Borna disease virus (BDV) upregulates expression of Calbindin D-28k.
Borna disease virus (BDV) is a neurotropic agent infecting distinct neuronal subpopulations in the central nervous system of various mammalian species possibly including humans. Horses, a major natural host for BDV, show gastrointestinal dysfunctions besides characteristic neurological symptoms. Therefore, we hypothesized that enteric neurons may be targets of BDV replication. The presence of BDV-specific antigen in subpopulations of the ENS was investigated. Four-week-old Lewis rats were infected intracerebrally and sacrificed 4-14 weeks post infection (p.i.). BDV-immunoreactive neurons were found in submucous and myenteric neurons of the proximal colon. Fourteen weeks p.i., the proportion of BDV-positive neurons was 44+/-17 and 24+/-7% in the submucous and myenteric plexus, respectively. The majority of BDV-positive myenteric neurons showed immunoreactivity for choline acetyltransferase. Expression of Calbindin D-28k (CALB) was found in 96% of submucous and 67% of myenteric BDV-immunoreactive neurons. Additionally, the number of CALB-immunoreactive neurons was significantly higher in the myenteric plexus of infected rats compared to controls. These data indicate that BDV infects specific subpopulations of enteric neurons. Therefore, the ENS might serve as a site for BDV replication and as an immunoprivileged reservoir for BDV. In addition, upregulation of CALB in neurons of the myenteric plexus is probably induced during BDV-infection.
Pfannkuche
Helga
H
Institute of Veterinary-Physiology, Faculty of Veterinary Medicine, An den Tierkliniken 7, Leipzig University, 04103 Leipzig, Germany. pfannku@rz.uni-leipzig.de
Konrath
Andrea
A
Buchholz
Ingeborg
I
Richt
Jürgen A
JA
Seeger
Johannes
J
Müller
Hermann
H
Gäbel
Gotthold
G
D000704:Analysis of Variance; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001890:Borna Disease / Q000821:virology*; D001891:Borna disease virus / Q000276:immunology / Q000472:pathogenicity*; D064026:Calbindins; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D007150:Immunohistochemistry; D009197:Myenteric Plexus / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods / Q000662:veterinary; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D064030:S100 Calcium Binding Protein G / Q000235:genetics* / Q000378:metabolism; D013368:Submucous Plexus / Q000473:pathology / Q000821:virology*; D015854:Up-Regulation
D000956:Antigens, Viral; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D002795:Choline O-Acetyltransferase