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DIFFERENTIATION-DEPENDENT SUSCEPTIBILITY OF HUMAN MUSCLE CELLS TO ZIKA VIRUS INFECTION
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Abstract
Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis,
and chikungunya viruses, that may be involved in the physiopathological course of the
infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently
reported symptoms. We investigated the susceptibility of human muscle cells to
ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated
into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast,
myotubes were shown to be resistant to ZIKV infection, suggesting a differentiationdependent
susceptibility. Infection was accompanied by a caspase-independent cytopathic
effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was
performed 24h and 48h post-infection in cells infected with two different isolates. Proteome
changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation
of the Interferon type I pathway, and a downregulation of protein synthesis. This work
constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection,
and differentiation-dependent restriction of infection from myoblasts to myotubes.
Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in
muscle tissue, the infection of muscle cells and the viral-induced alterations observed here
could have consequences in ZIKV infection pathogenesis.
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