Student who wish to enroll into the course part and receive ECTS should contact Anna H. Christensen at the seminar to sign up. To get ETCS it is mandatory to participate in the student session after the seminar.

Impact of type I IFN responses during viral encephalitis in the zebrafish 

Viral encephalitis is the consequence of infection of the brain or spinal cord parenchyme by a neuroinvasive virus. It is not uncommon in neonates with an estimated incidence of 1 million yearly cases worldwide, mostly due to herpes viruses (HSV-1 and 2) but also to various arboviruses including some responsible for recent pandemics such as chikungunya virus (CHIKV). Viral encephalitis has devastating consequences, often resulting or death or severe, long-term neurological impairment. These adverse effects are caused by the cytopathic effect of the virus itself, but also by the immune response it induces. This double-edged aspect of neuroinflammation, which limits viral spread but is also deleterious to the central nervous system (CNS) makes it particularly difficult to manage.

To address this largely unmet clinical issue, we have developed models of viral encephalitis in a genetically tractable and optically accessible model host, the zebrafish (Danio rerio). There are high overall similarities of zebrafish and human nervous and immune systems, and we previously have extensively characterized their type I interferon (IFN)-mediated response, including a core set of ~100 ancestral IFN-stimulated genes (ISG). We have also developed various transgenic and mutant zebrafish lines allowing us to image and manipulate this antiviral response. We simultaneously follow the spread of the viral infection in real time with fluorescent reporter viruses.

Using Sindbis virus (SINV), an alphavirus closely related to CHIKV, we have shown that this virus uses axonal transport to enter the CNS. When SINV is injected in peripheral tissue, it will invade the CNS in two to three days, using a route that depend on the initial inoculation site, and thus can be controlled. Injection in the caudal muscle results in spinal cord invasion via both sensory and motor neurons; however, the sensory route is more likely to ultimately result in brain invasion. Peripheral infection is readily controlled by the host IFN response; by contrast, CNS infection is more persistent and sometimes unstoppable. Imaging and mathematical modeling reveal a key role for the localization of the IFN response in these different outcomes in periphery and CNS, probably as a tradeoff between the need to restrict viral persistence in the CNS and limit adverse effects. 

We are currently trying to tease out the respective roles of the virus itself and the host response on the developing zebrafish brain. One particularly important future goal will be to identify approaches to limit neurological sequelae after antiviral treatment of an established encephalitis, both in the SINV and HSV-1 models.

Again student who wish to enroll into the course part and receive ECTS should contact Anna H. Christensen at the seminar to sign up. To get ETCS it is mandatory to participate in the student session after the seminar. 

See you there 

Rune and Yuya