Coxsackievirus-induced chronic inflammatory myopathy: virus variants distinguish between acute cytopathic effects and pathogenesis of chronic disease.
Infection with the Tucson strain of coxsackievirus B1 (CVB1T) causes the development of chronic inflammatory myopathy (CIM) and hind limb weakness in susceptible strains of mice. In this study, a panel of six plaque-purified viruses exhibiting either small or large plaque phenotypes was derived from parental CVB1T and parental CVB1T that had been passaged through monkey kidney cells. All six variants caused similar acute histopathology in muscle, but three of four passaged viruses (AMP1, AMP2, and AMP3) did not induce CIM while the fourth (MP3) caused some hind limb weakness but without associated muscle inflammation. In contrast, both viruses (MP1 and MP2) isolated directly from the parental CVB1T stock were myopathic. Large plaque MP2 caused higher mortality and more rapid inhibition of host cell biosynthesis, but both MP1 and MP2 induced CIM that was comparable to that induced by parental CVB1T. Plaque size was a stable characteristic of the variants but did not correlate with their ability to induce CIM. Five of the six variants showed equivalent levels of replication in muscle, monkey kidney cells, and GB myoblasts while one, AMP3, was selectively impaired for replication. Receptor binding and virus-induced inhibition of host cell transcription and translation were not linked to myopathogenicity. Thus, most of the passaged variants are robust infectious viruses, suggesting that viral induction of CIM does not depend solely on cytopathogenicity during the acute infection.
Tam
P E
PE
Department of Medicine, University of Minnesota, Minneapolis 55455, USA. tamxx001@maroon.tc.umn.edu
Messner
R P
RP
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D003384:Coxsackievirus Infections / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D003588:Cytopathogenic Effect, Viral; D029822:Enterovirus B, Human / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D014644:Genetic Variation; D007249:Inflammation / Q000503:physiopathology / Q000821:virology; D051379:Mice; D018908:Muscle Weakness / Q000503:physiopathology / Q000821:virology; D009220:Myositis / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D014176:Protein Biosynthesis; D011991:Receptors, Virus / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence
D011991:Receptors, Virus