T Cell-, Interleukin-12-, and Gamma Interferon-Driven Viral Clearance in Measles Virus-Infected Brain Tissue

Abstract

Genetic studies with immunocompetent mice show the importance of both T cells and gamma interferon (IFN-␥A wide variety of RNA and DNA viruses, including measles virus (MV), West Nile virus (WNV), human immunodeficiency virus, human cytomegalovirus, herpes simplex virus type 1 (HSV-1) and HSV-2, rabies virus, poliovirus, and lymphocytic choriomeningitis virus, cross the blood-brain barrier, infect the central nervous system (CNS), and cause encephalitis in mammals (3,15,26,29,34,35,75,82,85). A suitable combination of host inflammatory factors and the blood-borne viral load enables most viruses to enter the CNS. However, in the vast majority of cases, neuronal infection does not lead to overt CNS disease (82). Viral encephalitis detection rates, even when symptoms are severe, are very low (46), due in part to the poor sensitivity of the tools used to detect infection (21). However, with the increase in the number of immunocompromised individuals, whether through increasing populations of AIDS patients or pharmacologically compromised tissue transplant recipients, there has been a concomitant increase in viral encephalitis (11,77). Some viral infections, rather than being cleared by the host's immune system, result instead in high morbidity or mortality, often accompanied by severe inflammation (18,68,81). The balance between whether the adaptive immune response to a specific viral infection is protective or harmful is delicate, as many of the mechanisms that mediate inflammation in the CNS in both settings are similar (6,12,31,65).MV infection manifests itself primarily as a childhood illness with a characteristic macropapular rash. Measles is associated with high morbidity and mortality in developing countries, mostly due to a transient immunosuppression that leaves infected individuals highly susceptible to secondary infections (61). In approximately 0.1% of the cases, MV also causes CNS complications; one of these, subacute sclerosing panencephalitis (SSPE), is a progressive fatal disease. MV-associated encephalitis is one of many viral brain infections that cause high morbidity and mortality (26,34,85). The delayed pathogenesis of SSPE, including the route of viral entry into the CNS, is poorly understood (49). Although it is widely accepted that MV infection in the brain leads to complications, this is not necessarily the case, as MV mRNA is detected in the brains of 20% of individuals with no CNS pathology (33,34). It is currently hypothesized that SSPE is a result of mutated, aberrant

Cytolytic effector pathways and IFN‐γ help protect against Japanese encephalitis

“…The finding further underscores disparities in immune protection between the closely related flaviviruses . Overall, our results were consistent with a model of noncytolytic virus clearance from the CNS by IFN‐γ secreted from infiltrating T cells (reviewed in ), and place JEV in a heterogeneous group of neurotropic viruses that are controlled by IFN‐γ in the CNS, including Sindbis , mouse hepatitis , Theiler's murine encephalomyelitis , Borna disease , dengue and measles viruses . While our finding in mice was consistent with a reported protective role of IFN‐γ in human JE , it would be of considerable interest if noncytolytic virus clearance mediated by the cytokine also contributed to recovery from human neurotropic virus infection.…”

MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile

“…The products of these genes may play a critical role in inhibition of viral spread into non-infected cells and interference of viral replication in the infected cells [44]. IFNγ, on the other hand, is known to mediate its effect via the JAK-STAT signaling pathway leading to the subsequent activation of macrophages and NK cells, and expression of specific major histocompatibility complex proteins [45,46]. A study by Zhou et al [47] showed that infection of human monocyte-derived macrophages with MERS-CoV induced the expression of IFN-γ and the subsequent expression of major histocompatibility complex class-I genes [47].…”

CD4 and CD8 T cells mediate distinct lethal meningoencephalitis in mice challenged with Tacaribe arenavirus

“…T cells reduce the susceptibility of mice to many CNS viral infections such as measles and West Nile virus; 47, 48, 49, 50, 51 however, T-cell-mediated damage to the CNS has been described in LCMV and BDV. 52,46 The studies presented here show that TCRV infection in T-cell sufficient animals results in significant infiltration of T cells and monocytes into the parenchyma of the CNS, while T-cell-deficient mice (CD3ɛ KO) develop only a mild inflammation with marginal increases in the expression of chemokines and proinflammatory cytokines (Figure 3aii).…”