Abstract
Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.
Highlights
Measles is a highly contagious human disease caused by acute infection with measles virus (MV) and remains an important cause of child morbidity and mortality worldwide[1]
To determine whether or not mutations in the viral genome are dispensable for the establishment of persistent MV infection, we analysed cells and viruses during the early phase of persistent MV infection in cultured cells
We presented one of the possible mechanisms by which MV establishes long-term persistent infection without mutations in the viral genome
Summary
Measles is a highly contagious human disease caused by acute infection with measles virus (MV) and remains an important cause of child morbidity and mortality worldwide[1]. Matrix protein (M) is involved in virion budding from the infected cell. MV is highly cytopathic and commonly causes acute severe infection, resulting in measles and, for one out of 1,000 measles cases, acute demyelinating encephalitis. MV has the potential to cause persistent infection, the occurrence of these diseases is very low and MV persistence has only been found in the brain in these cases. The persistent infection with MV in SSPE has been assumed to be a result of the appearance of mutant viruses, www.nature.com/scientificreports/. The persistently infected cells show characteristic features, such as a disappearance of the cytopathic effect, a marked reduction in cell-free virion production, and a resistance to superinfection by closely related viruses. Interferon (IFN) was suggested to be involved in persistent infection with MV, through restricting viral replication[20]. Despite the proposition of several possibilities, the mechanisms responsible for MV persistent infection are still under debate
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
