| First Author | McWilliams IL | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 7 | Pages | 1718-1726.e4 |
| PubMed ID | 30759384 | Mgi Jnum | J:286909 |
| Mgi Id | MGI:6390108 | Doi | 10.1016/j.celrep.2019.01.069 |
| Citation | McWilliams IL, et al. (2019) Pseudovirus rVSVDeltaG-ZEBOV-GP Infects Neurons in Retina and CNS, Causing Apoptosis and Neurodegeneration in Neonatal Mice. Cell Rep 26(7):1718-1726.e4 |
| abstractText | Zaire Ebola virus (ZEBOV) survivors experience visual and CNS sequelae that suggests the ZEBOV glycoprotein can mediate neurotropism. Replication-competent rVSVDeltaG-ZEBOV-GP vaccine candidate is generally well tolerated; however, its potential neurotropism requires careful study. Here, we show that a single inoculation of rVSVDeltaG-ZEBOV-GP virus in neonatal C57BL/6 mice results in transient viremia, neurological symptoms, high viral titers in eyes and brains, and death. rVSVDeltaG-ZEBOV-GP infects the inner layers of the retina, causing severe retinitis. In the cerebellum, rVSVDeltaG-ZEBOV-GP infects neurons in the granular and Purkinje layers, resulting in progressive foci of apoptosis and neurodegeneration. The susceptibility to infection is not due to impaired type I IFN responses, although MDA5(-/-), IFNbeta(-/-), and IFNAR1(-/-) mice have accelerated mortality. However, boosting interferon levels by co-administering poly(I:C) reduces viral titers in CNS and improves survival. Although these data should not be directly extrapolated to humans, they challenge the hypothesis that VSV-based vaccines are non-neurotropic. |
