The Immune Response in Measles: Virus Control, Clearance and Protective Immunity

Abstract

Measles is an acute systemic viral infection with immune system interactions that play essential roles in multiple stages of infection and disease. Measles virus (MeV) infection does not induce type 1 interferons, but leads to production of cytokines and chemokines associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling and activation of the NACHT, LRR and PYD domains-containing protein (NLRP3) inflammasome. This restricted response allows extensive virus replication and spread during a clinically silent latent period of 10-14 days. The first appearance of the disease is a 2-3 day prodrome of fever, runny nose, cough, and conjunctivitis that is followed by a characteristic maculopapular rash that spreads from the face and trunk to the extremities. The rash is a manifestation of the MeV-specific type 1 CD4⁺ and CD8⁺ T cell adaptive immune response with lymphocyte infiltration into tissue sites of MeV replication and coincides with clearance of infectious virus. However, clearance of viral RNA from blood and tissues occurs over weeks to months after resolution of the rash and is associated with a period of immunosuppression. However, during viral RNA clearance, MeV-specific antibody also matures in type and avidity and T cell functions evolve from type 1 to type 2 and 17 responses that promote B cell development. Recovery is associated with sustained levels of neutralizing antibody and life-long protective immunity.

Keywords: antibody maturation; inflammasome; rash; viral RNA persistence.

Figure 1

Schematic diagram of measles virus (MeV) clearance and immune responses in rhesus macaques. Infection with wild type (WT) MeV results in viremia (infectious virus) and rash. The rash is associated with appearance of interferon (IFN)-γ-producing T cells that decline quickly after the viremia is cleared. There is a prolonged phase of slow viral RNA clearance from peripheral blood mononuclear cells (PBMCs) with persistence of viral RNA in lymph nodes (LN). During RNA clearance antibody increases in amount and avidity. Waves of MeV-specific T cells continue to appear in circulation with a shift from IFN-γ production to interleukin 17 (IL-17) production. Data graphed from Lin et al. [9,20].

Figure 2

Time course for production of MeV-specific immunoglobulin G (IgG) and maturation of antibody avidity after infection. (A) Binding IgG antibody to MeV as determined by enzyme immunoassay; (B) Avidity of the antibody from panel A as measured by ammonium thiocyanate elution. Red boxes indicate the period of the rash. Data graphed from Pan et al. [65].