Measles virus antigen in macrophage/microglial cells and astrocytes of subacute sclerosing panencephalitis

Abstract

de Siqueira, M. M. Measles virus antigen in macrophage/microglial cells and astrocytes of subacute sclerosing panencephalitis. APMISIn two patients with subacute sclerosing panencephalitis (SSPE) of 10 and 25 months duration we demonstrated by immunohistochemistry the presence of measles-virus nucleocapsid antigen (MVNA) in CD68+ cells and astrocytes of brain tissues. In both cases, CD68+ hematogenous monocyte/ macrophages and perivascular microglial cells (MO) were found infiltrating the brain parenchyma, and often partially or completely invested by perivascular reactive astrocytes expressing glial fibrillary acidic protein (GFAP). MO with cytoplasmic MVNA were often seen in the Virchow-Robin spaces and in close association with perivascular astrocytes, which often also contained MVNA+ intracytoplasmic inclusions. Reactive astrocytosis was more severe in the patient with long-standing illness, and a correspondingly elevated number of strongly GFAP+ MVNA+ or MVNA-perivascular binucleated astrocytes was observed. An uptake of MVNA+ cell debris by reactive astrocytes was evident in areas of white matter displaying extensive demyelination and necrosis. Taken together, these observations seem to indicate that the brain infiltration by M@ carrying measles virus could represent one pathway of virus entry and dissemination in the central nervous system. Virus transfer to perivascular astrocytes via cell-to-cell contacts with infected macrophages is also suggested.Subacute sclerosing panencephalitis (SSPE) is a rare subacute infection of the central nervous system (CNS) in children and adolescents caused by measles virus (MV) (40). This usually fatal, slowly progressing virus encephalitis occurs several years after primary MV infection (1 5 , 40) and is characterized by uncontrolled intrathecal replication of mutated and defective MV in neuronal and glial cells (for review see

Measles Virus-Induced Disruption of the Glial-Fibrillary-Acidic Protein Cytoskeleton in an Astrocytoma Cell Line (U-251)

“…MV infection of the central nervous system (CNS) is a rare event (27,30). Oligodendrocytes and neurons are the predominantly infected cell types, although infected astrocytes have also been described (1,30,31,34). In this study we have used two astrocytoma cell lines, the first being GCCM cells, which have been used to study MV cell-to-cell spread (13a).…”

Roles of Macrophages in Measles Virus Infection of Genetically Modified Mice

“…Moreover, dendritic cells (DC) can be infected in vitro (11,14,34). In cases where the virus disseminates in the central nervous system (13), CD68-positive hematogenous macrophages/microglia cells are infected (25).…”

Rapid Progressive Subacute Sclerosing Panencephalitis in a 2-Year-Old Child with Congenital Athyreosis

“…The invariably fatal disease occurs several years after primary MV infection [2] and is characterized by uncontrolled replication of mutated and defective MV in neuronal and glial cells [3]. MV infection that occurs before 2 years of age is associated with a risk for SSPE that is 16 times as high as the risk associated with infection after 5 years of age [4].…”

“…Although congenital hypothyreosis has been associated with a variable degree of impaired immune function, there were no clinical signs of immunodeficiency in our patient. Molecular-biological investigations have revealed that the persistence of MV in the CNS is associated with and most likely caused by a defective viral replication, which allows MV to survive intracellularly during incubation period while remaining inaccessible to host immune surveillance [3,12]. The susceptibility of the host, as well as the host's age and immune status, at the time of infection also constitute significant factors for disease progression [12].…”

“…In 1974, Walton and Valverde reported a series of 4 American soldiers in Panama who had a defined history of exposure to Leishmania species in an area of endemicity, followed by an extended period living in a nonendemic location. After sustaining relatively minor trauma (a puncture wound of the hand, an eyelid struck by a small piece of gravel, a pimple that was manipulated, and a repeatedly abraded elbow) each patient developed a leishmanial lesion at the site of trauma [3]. In a different publication, Walton presented a dramatic photograph of a leishmanial lesion that developed along the margins of the length of a laceration [4].…”