Single-cell profiling of immune activation, dysregulation, and reconstitution in rhesus macaques after measles virus infection

Abstract

Protective immunity is induced by both, wild-type measles virus (WT MeV) and live-attenuated (LA) measles virus vaccine (LAMV), affording the opportunity to compare common and selective immunological underpinnings of immune protection. Here, peripheral blood mononuclear cells (PBMCs) were collected from rhesus macaques at several timepoints after infection with either virus for single-cell RNA/VDJ sequence analysis. Data revealed acute immune activation at 10/11 days post infection (dpi) with WT MeV, with increased frequencies of CD8 T cells, monocytes and NK cells, and B and T cell expansion and activation, most notably IgA+ B cells and cytotoxic CD8 T cells. Two interferon-stimulated genes (ISGs), IFI6 and IFI27, were upregulated selectively across PBMCs, with strongest ISGylation and JAK-STAT activation in monocytes. Furthermore, WT MeV-infected PBMCs were enriched among IgA+ B cells and Th17 CD4 T cells, expressing the highest levels of ISGs. However, lymphocyte depletion, with absolute or relative reduction in B, CD4, and CD8 T cells, preferential ISG expression in activated/memory but not naive B and T cells, as well as dampened acute NK cell activation suggested acute immune suppression. Subsequent immune reconstitution was implicated by increased frequencies of IgM+ memory B cell subtypes with lower IGHV somatic hypermutation (SHM) rates at 42/43/56 dpi. LAMV elicited distinct humoral and cellular responses, with greater induction of IgG+ than IgA+ B cells and differential cytotoxic CD8 T cells encoding distinct TRBV/TRAV genes, compared to WT MeV. LAMV infection induced no signs of immune suppression. Together, these data provide insights into distinct features of WT MeV and LAMV-induced immunity.