Comparative analysis of central nervous system persistence of morbilliviruses across host species reveals shared features with subacute sclerosing panencephalitis

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare but always fatal neurological complication of measles, associated with persistent measles virus (MeV) infection of the central nervous system (CNS). MeV is detected in the brains of deceased SSPE patients as hypermutated viral genomes, which often contain premature stop codons in the matrix (M) gene and encode a hyperfusogenic fusion (F) protein. As a result, infected cells in the CNS cannot produce virions but rather transmit the viral ribonucleoprotein from cell-to-cell in a slow but progressive manner, which ultimately results in widespread MeV infection of the brain. However, our understanding of the pathogenesis of SSPE is constrained by the lack of animal models combined with a clinically silent incubation period of several years. MAIN TEXT: In a recent publication in PNAS, Daniel Roji et al. analysed animal morbillivirus sequences detected in the brains of persistently infected hosts, including a lynx (canine distemper virus, CDV), two seals (phocine distemper virus, PDV) and a dolphin (cetacean morbillivirus, CeMV). The authors describe that the morbillivirus sequences detected in these animals contained unique mutational signatures. The CDV, CeMV and one of the PDV sequences encoded nonfunctional M proteins and hyperfusogenic F proteins, reminiscent of the mutational profile of MeV detected in SSPE patients. Therefore, the authors conclude that human and animal morbilliviruses associated with chronic neurological infections share key genotypic and phenotypic traits, and that thorough analysis of naturally occurring animal morbillivirus infections could improve our understanding of SSPE pathogenesis. CONCLUSION: The comparison of neurological complications associated with human and animal morbillivirus infections as described by Daniel Roji et al. provides a unique One Health approach to understanding the drivers of SSPE. These findings may support the development of early diagnostics or an animal model for SSPE, providing an opportunity to test novel intervention strategies.