Zika virus replicates in skeletal muscle contributing to peripheral viral amplification prior to reach neural tissue

Zika virus (ZIKV) infections are still a worldwide concern due to the severity of neurological outcomes. ZIKV neurotropism is well characterized, but peripheral tissue could be sites of viral amplification, contributing to endothelial-barrier crossing and access to peripheral nerves. During acute and late phases of infection, ZIKV can be detected in several body fluids, eyes, testis and vagina. However, the importance of initial replication sites for the establishment of infection and viral spread remain unknown. Here we demonstrated that ZIKV replicates primarily in human muscle precursor cells, resulting in cell death and inhibition of myogenesis. ZIKV also replicates in fetal muscle after maternal transmission and in infected neonate mice, inducing lesions and inflammation. Muscle was an important site of viral amplification, sustaining higher peripheral viral loads than liver and spleen. In addition, ZIKV showed rapid and sustained replication kinetics in muscle even before replication in the neural tissues, persisting until 16 days post infection. Our results highlight the importance of muscle in ZIKV pathogenesis as a peripheral site of viral amplification which may contribute to ZIKV reaching neural structures.