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Tissue tropism of recombinant coxsackieviruses in an adult mouse model

¹ Department of Virology and MediCity Research Laboratory, University of Turku, FIN-20520 Turku, Finland
² Department of Pathology, University of Helsinki and Helsinki University Hospital, FIN-00014 Helsinki, Finland
³ Department of Pathology, University of Uppsala, Uppsala, Sweden
⁴ Division of Immunologic and Infectious Diseases, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
⁵ Department of Biological Sciences, University of Essex, CO4 3SQ Colchester, UK
⁶ Department of Medical Microbiology, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland

Correspondence
Heli Harvala
h.harvala{at}vir.gla.ac.uk

Recombinant viruses, constructed by exchanging the 5' non-coding region (5'NCR), structural and non-structural protein coding sequences were used to investigate determinants responsible for differences between coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) infections in adult mice and two cell lines. Plaque assay titration of recombinant and parental viruses from different tissues from adult BALB/c mice demonstrated that the structural region of CBV3 determined tropism to the liver tissue due to receptor recognition, and the 5'NCR of CBV3 enhanced viral multiplication in the mouse pancreas. Infection with a chimeric virus, containing the structural region from CBV3 and the rest of the genome from CAV9, and the parental CBV3 strain, caused high levels of viraemia in adult mice. The ability of these viruses to infect the central nervous system suggested that neurotropism is associated with high replication levels and the presence of the CBV3 capsid proteins, which also enhanced formation of neutralizing antibodies. Moreover, the appearance of neutralizing antibodies correlated directly with the clearance of the viruses from the tissues. These results demonstrate potential pathogenicity of intraspecies recombinant coxsackieviruses, and the complexity of the genetic determinants underlying tissue tropism.

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