Understanding the causes and consequences of measles virus persistence

Abstract

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10-14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity.

Keywords: RNA; lymphoid tissue; measles; viruses.

Figure 1.. Schematic diagram of viral and immunologic features of measles during the first 3–4 months after infection.

Viremia is the period during which infectious virus can be recovered from peripheral blood mononuclear cells (PBMCs). Viral RNA is cleared from PBMCs within 2–3 months but persists in lymph nodes (LNs) .

Figure 2.. Innate immune responses to wild-type measles virus infection in humans and macaques.

Measurement of levels of cytokines indicative of nuclear factor kappa B activation ( A) and inflammasome activation ( B) in plasma of children and interferon ( C) in monkeys at the time of rash onset ^, .