Tissue tropism of recombinant coxsackieviruses in an adult mouse model.
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.
Harvala
Heli
H
Department of Virology and MediCity Research Laboratory, University of Turku, FIN-20520 Turku, Finland.
Kalimo
Hannu
H
Department of Pathology, University of Uppsala, Uppsala, Sweden.|Department of Pathology, University of Helsinki and Helsinki University Hospital, FIN-00014 Helsinki, Finland.
Bergelson
Jeffrey
J
Division of Immunologic and Infectious Diseases, The Children's Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA.
Stanway
Glyn
G
Department of Biological Sciences, University of Essex, CO4 3SQ Colchester, UK.
Hyypiä
Timo
T
Department of Medical Microbiology, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland.|Department of Virology and MediCity Research Laboratory, University of Turku, FIN-20520 Turku, Finland.
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D002460:Cell Line; D029822:Enterovirus B, Human / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000473:pathology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D010179:Pancreas / Q000821:virology; D011995:Recombination, Genetic; D013116:Spinal Cord / Q000821:virology; D010948:Viral Plaque Assay; D015678:Viral Structural Proteins / Q000235:genetics* / Q000378:metabolism; D014766:Viremia / Q000821:virology
D020121:5' Untranslated Regions; D015678:Viral Structural Proteins