Mutations in the rotavirus spike protein VP4 reduce trypsin sensitivity but not viral spread
Key result
The D/128 rotavirus mutant with VP4 mutations is approximately 10-fold less sensitive to trypsin proteolysis than wild-type virus, yet replicates with identical kinetics.
Population
Rotavirus isolate cultured in the absence of trypsin and wild-type (WT) rotavirus
Comparison
Substitution mutation in the spike protein VP4 vs Wild-type (WT) rotavirus
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Altered VP4 trypsin sensitivity does not impair replication in vitro; leaves open effects on rotavirus pathogenesis in animal models.
Structured PICO
P
Population
Rotavirus isolate cultured in the absence of trypsin and wild-type (WT) rotavirus
E
Exposure
Substitution mutation in the spike protein VP4
C
Comparator
Wild-type (WT) rotavirus
O
Outcome
Proteolysis resistance, kinetics of membrane penetration-associated conformational change, and viral replicationsurrogate
Mutations in the rotavirus spike protein VP4 that reduce trypsin sensitivity and slow conformational changes do not impair viral replication, providing new insights into viral cell entry.
Limitations
- The in vitro kinetics reported may not be directly comparable to in vivo membrane penetration steps.
- Additional kinetic studies including liposomes are needed to fully understand VP5* function.
Cite This Study
Trask et al. (2013) studied Rotavirus infection. D/128 rotavirus strain (VP4 mutations R241T and N477S) vs. SA11 (WT) rotavirus strain was evaluated on Trypsin sensitivity and viral spread kinetics. The D/128 rotavirus mutant with VP4 mutations is approximately 10-fold less sensitive to trypsin proteolysis than wild-type virus, yet replicates with identical kinetics.