The Open Virology Journal

2013, 7 : 49-56
Published online 2013 April 5 . DOI: 10.2174/1874357901307010049
Publisher ID: TOVJ-7-49

RESEARCH ARTICLE
Tropism Analysis of Two Coxsackie B5 Strains Reveals Virus Growth in Human Primary Pancreatic Islets but not in Exocrine Cell Clusters In Vitro

Hodik M, * , Lukinius A , Korsgren O and Frisk G
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

* Address correspondence to this author at the Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Rudbecklaboratoriet, Dag Hammarskjöldsväg 20, 751 85 Uppsala, Sweden; Tel: +46735720471; Fax: +46 (18) 611 02 22; E-mail: monika.hodik@igp.uu.se

ABSTRACT

Human Enteroviruses (HEVs) have been implicated in human pancreatic diseases such as pancreatitis and type 1 diabetes (T1D). Human studies are sparse or inconclusive and our aim was to investigate the tropism of two strains of Coxsackie B virus 5 (CBV-5) in vitro to primary human pancreatic cells. Virus replication was measured with TCID50 titrations of aliquots of the culture medium at different time points post inoculation. The presence of virus particles or virus proteins within the pancreatic cells was studied with immunohistochemistry (IHC) and electron microscopy (EM). None of the strains replicated in the human exocrine cell clusters, in contrast, both strains replicated in the endocrine islets of Langerhans. Virus particles were found exclusively in the endocrine cells, often in close association with insulin granules. In conclusion, CBV-5 can replicate in human endocrine cells but not in human exocrine cells, thus they might not be the cause of pancreatitis in humans. The association of virus with insulin granules might reflect the use of these as replication scaffolds.

Keywords:

Coxsackie B virus, human enterovirus, human enterovirus capsid protein 1, human islets of langerhans, pancreas, pancreatitis, type 1 diabetes..