Zika virus infection disturbs development of human muscle progenitor cells

Zika virus (ZIKV) infection has emerged as a global public health emergency due to its expansion capacity and ability to cause neurological and congenital diseases. Muscle cells are targets for ZIKV, and myalgia and muscle disorders are frequently related symptoms during infection. We have previously demonstrated that myoblasts, the proliferating muscle stem cells essential for muscle repair, are permissive to ZIKV infection, generating infectious viral particles. In contrast, differentiated myotubes, derived from myoblast differentiation and fusion, control ZIKV replication. Nevertheless, little is known about the impact of ZIKV infection on muscle myogenesis. Using an <i>in vitro</i> model of skeletal muscle regeneration, human myoblasts were infected with the ZIKV-Rio-U1 strain, and their proliferation, adhesion, migration, and differentiation/fusion properties were analyzed 72 hours post-infection. We found that ZIKV replicates within myoblasts, promoting biological alterations such as the inhibition of cell cycle progression, preventing cell proliferation. Infected myoblasts exhibit poor adhesion, lack of membrane elongation, a reduced cell area, and decreased migratory capacity. Moreover, infection impaired the fusion of human myoblasts. Although differentiated and fused myotubes control ZIKV infection, proliferating infected myoblasts present an altered myogenic program. These results strongly suggest that ZIKV infection can affect myogenesis, modulating key biological processes crucial for skeletal muscle differentiation and regeneration. Accordingly, it is conceivable that ZIKV infection may impact myogenesis during embryogenesis, growth, and subsequent regenerative episodes during the adult period.