Abstract
Measles is an acute viral disease associated both with immune suppression and development of life-long immunity. Clearance of measles virus (MeV) involves rapid elimination of infectious virus during the rash followed by slow elimination of viral RNA. To characterize cellular immune responses during recovery, we analyzed the appearance, specificity and function of MeV-specific T cells for 6 months after respiratory infection of rhesus macaques with wild type MeV. IFN-γ and IL-17-producing cells specific for the hemagglutinin and nucleocapsid proteins appeared in circulation in multiple waves approximately 2-3, 8 and 18–24 weeks after infection. IFN-γ-secreting cells were most abundant early and IL-17-secreting cells late. Both CD4+ and CD8+ T cells were sources of IFN-γ and IL-17, and IL-17-producing cells expressed RORγt. Therefore, the cellular immune response evolves during MeV clearance to produce functionally distinct subsets of MeV-specific CD4+ and CD8+ T cells at different times after infection.
Highlights
Measles is a highly contagious viral disease that remains an important cause of childhood morbidity and mortality[1] with most deaths due to secondary infections[2, 3]
To document the time course of clearance of infectious virus and viral RNA in this cohort of 3-year old macaques, infectious virus in the blood was monitored by co-cultivation of peripheral blood mononuclear cells (PBMCs) with Vero/hSLAM cells and viral RNA was quantified by RT-qPCR
These data confirm that prolonged presence of viral RNA is characteristic of primary measles virus (MeV) infection[7]
Summary
Measles is a highly contagious viral disease that remains an important cause of childhood morbidity and mortality[1] with most deaths due to secondary infections[2, 3]. The host adaptive immune response is necessary for control and clearance of virus[8, 9] and both MeV-specific antibody and T cells contribute to gradual clearance of viral RNA from PBMCs7. Studies of both humans and monkeys suggest that CD8+ T cells are important for clearance of infectious virus during the rash. Because it is likely that the functional evolution of T cell subsets during the prolonged phase of MeV RNA clearance is important for eventual virus clearance, immune suppression and establishment of life-long protective immunity, we characterized cellular immune responses to MeV over a period of six months after infection of rhesus macaques with a wild type strain of MeV
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