Pathogenesis of coxsackievirus A9 in mice: role of the viral arginine-glycine-aspartic acid motif.
Coxsackievirus A9 (CAV9) contains an arginine-glycine-aspartic acid (RGD) motif which participates in cell entry. Mutants with alterations in the RGD-containing region were utilized to explore the importance of the tripeptide in the pathogenesis of CAV9 in mice. Using in situ hybridization, the parental CAV9 strain was observed to infect skeletal muscle (intercostal, platysma, lingual and thigh muscles) of newborn mice, whereas the RGD-less mutants were detectable only in platysma and lingual muscles. In addition, newborn mice infected with the mutants survived longer than CAV9-infected mice. In adult mice, the parental strain of CAV9, but not the mutants, achieved moderately high titres in the pancreas. These results suggest that the RGD motif has a significant role in the pathogenesis of CAV9 in mice but also that RGD-independent entry routes can be utilized in the infection of murine tissue.
Harvala
Heli
H
Department of Virology and MediCity Research Laboratory, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland.
Kalimo
Hannu
H
Department of Pathology, University of Turku and Turku University Hospital, FIN-20520 Turku, Finland.
Stanway
Glyn
G
Department of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK.
Hyypiä
Timo
T
Department of Medical Microbiology, University of Oulu, FIN-90014 Oulu, Finland.|Department of Virology and MediCity Research Laboratory, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland.
D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000821:virology*; D005998:Glycine / Q000235:genetics; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000821:virology; D009154:Mutation; D009928:Organ Specificity; D010179:Pancreas / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D013997:Time Factors
D012367:RNA, Viral; D001224:Aspartic Acid; D001120:Arginine; D005998:Glycine