Quantitative analysis of viral RNA kinetics in coxsackievirus B3-induced murine myocarditis: biphasic pattern of clearance following acute infection,with persistence of residual viral RNA throughout and beyond the inflammatory phase of disease

Although the association remains controversial, enteroviruses have been imp licated in the aetiology of several chronic diseases of humans, To further understand the mechanism of enterovirus persistence and its relationship to organ pathology, virus infectivity and viral RNA kinetics in the heart and other target organs during acute and persistent phases of murine coxsackie virus 83 infection were investigated. These studies revealed a biphasic pat tern of virus clearance. Thus, there was a rapid but incomplete clearance o f viral RNA from the myocardium following the acute phase of virus replicat ion, which paralleled the elimination of virus infectivity. The mean half-l ife of viral RNA between days 5 and 14 post-infection (p.i.) was 13.4 h, In contrast, a much slower rate of decline in viral RNA levels was observed d uring the post-infectious inflammatory phase of myocarditis, The mean half- life of viral RNA between days 14 and 90 p.i. was 14.1 days, Viral RNA pers isted in the myocardium beyond the resolution of inflammation and was still detectable in a proportion of animals 90 days after infection, Clearance o f viral RNA from other target organs occurred more rapidly, but the rate of clearance was largely independent of the level of viral RNA present during the acute phase of infection. Thus, while antiviral immune responses effec tively eliminated infectious virus, clearance of residual viral RNA from th e myocardium and other target organs was significantly delayed, despite a p rolonged inflammatory response. These findings suggest that clearance of pe rsistent enterovirus infection requires mechanisms different from those res ponsible for the elimination of virus infectivity.