Rotavirus Spike Protein VP4 Mediates Viroplasm Assembly by Association to Actin Filaments
Janine Vetter, Guido Papa, Michael Seyffert, Kapila Gunasekera, Giuditta De Lorenzo, Mahesa Wiesendanger, Jean‐Louis Reymond, Cornel Fraefel, Óscar R. Burrone, Catherine Eichwald
Abstract
The spike protein VP4 participates in diverse steps of the rotavirus (RV) life cycle, including virus-cell attachment, internalization, modulation of endocytosis, virion morphogenesis, and virus egress. Using reverse genetics, we constructed for the first time a recombinant RV, rRV/VP4-BAP, harboring a heterologous peptide in the lectin domain (loop K145-G150) of VP4. The rRV/VP4-BAP was replication competent but with reduced fitness due to a defect in the ability to reorganize the actin cytoskeleton, which affected the efficiency of viroplasm assembly. This defect was rescued by adding a permeable small-peptide mimicking the wild-type VP4 loop K145-G150. In addition to revealing a new role of VP4, our findings suggest that rRV harboring an engineered VP4 could be used as a new dual vaccination platform providing immunity against RV and additional heterologous antigens.