017 – Infection of the central nervous system by Zika virus in a murine model.

Electronic Poster | Session 1

017 – Infection of the central nervous system by Zika virus in a murine model.

William Enlow (1) – Maude Bordeleau (2) – Olus Uyar (1) – Jocelyne Piret (1) – Nathalie Vernoux (2) – Nathalie Goyette (1) – Julie Carbonneau (1) – Marie-Eve Tremblay (2) – Guy Boivin (1)
CHU de Québec, Université Laval, Axe Microbiologie, Immunologie et Infectiologie, Québec, Canada (1) – CHU de Québec, Université Laval, Axe Neurosciences, Québec, Canada (2)


Zika virus (ZIKV) is associated with the development of microcephaly in neonates as well as Guillain-Barré syndrome and other neurological disorders in adults. The role of microglia in the immune response to ZIKV infection of the central nervous system (CNS) is controversial. Some studies showed that microglia are activated following ZIKV infection of the CNS in mice and primates whereas others reported that microglia are highly susceptible to infection in vitro. Therefore, it is unknown whether microglia exhibit a beneficial or detrimental role in ZIKV infection of the CNS. Mice susceptible to ZIKV (TRIF-/-×IPS-1-/-) were infected intravenously (106 PFUs in 100 µL) before being sacrificed on days 0, 3, 7, 10 and 14 post-infection (pi) to collect blood and brain. The viral load was measured in serum and brain homogenates by ddPCR. Cytokine and chemokine levels in brain homogenates were determined by immunodetection (Luminex). Brain sections were stained to detect the virus, infiltrating monocytes/microglia (Iba1), and microglia (TMEM119) for immunohistochemistry (IHC), and immunofluorescence (IF) analyses. ZIKV distribution as well as microglial density, morphology and colocalization with ZIKV were determined from IHC and IF images. The viral load reached a peak level on day 7 pi (107 viral RNA copies/g of brain) and remained high through day 14. The inflammatory response (cytokine/chemokine levels) also peaked on day 7 pi in the brain. ZIKV IHC staining of brain sections was significantly stronger on day 10 pi and the dorsal hippocampus (dHPC) was the most infected region. IF staining revealed an increase in microglial density on day 7 pi in the dHPC. Additionally, ZIKV strongly colocalized with microglia in the dHPC. These results suggest that microglia contribute to the immune response to ZIKV while potentially sustaining infection. Further analyses in electron microscopy to analyse microglial morphology and phagocytosis are underway to ultimately determine their beneficial or detrimental contribution in ZIKV infection of the CNS.