Association of EV71 3C polymorphisms with clinical severity.

OBJECTIVES: Enterovirus 71 (EV71) may cause neurological and fatal cases. EV71 3C plays an important role on viral replication and possess proteolysis activity. To delineate pathogenesis of EV71 virulence, we studied EV71 3C genetics, protease activity and correlated the results with clinical severity.

METHODS: EV71 cases were collected; 3C of EV71 was sequenced and linked with clinical severity. 3C protease activity, viral replication rates of EV71 infectious clones with different 3C and 3C interaction with host proteins were analyzed.

RESULTS: The polymorphisms of EV71 3C at the 79th amino acid were associated with clinical severity. About 26% (62/234) patients infected by EV71 with wild-type 3C (T79) had neurological involvement but 78% (25/32) patients infected by EV71 with mutant 3C (T79V) did (p < 0.001). There was no significant difference of protease activity among the different 3C variants. EV71 with mutant 3C (T79V) had the highest viral replication rate and the mutant 3C (T79V) had weaker interaction with TRIM21, a component of antibody-dependent intracellular neutralization, than the other mutants (T79I and T79A).

CONCLUSION: We found that 3C polymorphisms were associated with clinical severity and viral replication, which might be related to 3C interaction with important host proteins such as TRIM21.