Mapping of tissue tropism determinants in coxsackievirus genomes.
Genomic regions responsible for the different tissue tropisms of coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) in newborn mice were investigated using recombinant viruses. Infectious cDNA clones of CAV9, a virus known to infect striated muscle, and CBV3, affecting the central nervous system, pancreas, liver, brown fat and striated muscle, were used to generate chimeric viruses. In situ hybridization analysis of different tissues from mice infected with the recombinant viruses, constructed by exchanging the 5' non-coding region (5'NCR), structural and non-structural genes, demonstrated that the pancreo- and liver tropism map predominantly to CBV3 sequences within the capsid genes, evidently due to receptor recognition. Although the major neurotropism determinant in the CBV3 genome was in the capsid region, viruses containing the CAV9 capsid were also able to initiate infection in the central nervous system provided they contained the CBV3 5'NCR. The presence of the 5'NCR of CAV9 clearly enhanced muscle tissue tropism.
Harvala
Heli
H
Department of Virology and MediCity Research Laboratory, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland1.
Kalimo
Hannu
H
Department of Pathology, University of Turku and Turku University Hospital, FIN-20520 Turku, Finland2.
Dahllund
Leif
L
Department of Virology and MediCity Research Laboratory, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland1.
Santti
Juhana
J
Department of Virology and MediCity Research Laboratory, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland1.
Hughes
Pamela
P
Department of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK3.
Hyypiä
Timo
T
Department of Virology, Haartman Institute, PO Box 21, FIN-00014 Helsinki, Finland4.|Department of Virology and MediCity Research Laboratory, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland1.
Stanway
Glyn
G
Department of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK3.
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002213:Capsid / Q000235:genetics; D002490:Central Nervous System / Q000821:virology; D003384:Coxsackievirus Infections / Q000503:physiopathology / Q000821:virology*; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D029822:Enterovirus B, Human / Q000235:genetics; D016679:Genome, Viral; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000821:virology; D009928:Organ Specificity; D010179:Pancreas / Q000821:virology; D011995:Recombination, Genetic
D020121:5' Untranslated Regions