Imaging of viral neuroinvasion in the zebrafish reveals that Sindbis and chikungunya viruses favour different entry routes

Gabriella Passoni, Christelle Langevin, Nuno Palha, Bryan C. Mounce, Valérie Briolat, Pierre Affaticati, Elodie De Job, Jean-Stéphane Joly, Marco Vignuzzi, Maria-Carla Saleh, Philippe Herbomel, Pierre Boudinot, Jean-Pierre Levraud

Alphaviruses, such as chikungunya (CHIKV) and Sindbis virus (SINV), are vector‑borne pathogens that cause acute illnesses in humans and are sometimes associated with neuropathies, especially in infants and elderly patients. Little is known about their entry mechanism in the central nervous system (CNS), even for SINV, which has been used extensively as a model for viral encephalopathies. We previously established a CHIKV infection model in the optically transparent zebrafish larva; here we describe a new SINV infection model in this host. We imaged in vivo the onset and the progression of the infection caused by intravenous SINV inoculation. Similar to that described for CHIKV, infection in the periphery was detected early and was transient, while CNS infection started at later time points and was persistent or progressive. We then tested the possible mechanisms of neuroinvasion by CHIKV and SINV. Neither virus relied on macrophage-mediated transport to access the CNS. CHIKV, but not SINV, always infects endothelial cells of the brain vasculature. By contrast, axonal transport was much more efficient with SINV than CHIKV, both from periphery to the CNS or between neural tissues. Thus, the preferred mechanisms of neuroinvasion by these two related viruses are distinct, providing a powerful imaging-friendly system to compare mechanisms and prevention methods of encephalopathies.