Glial fibrillary acidic protein (GFAP) immunochemical profile after Junin virus infection of rat cultured astrocytes

Iacono, Rubén Francisco; Aviñón, Analia Nessi de; Rosetti, F.; Berría, María I.

doi:10.1016/0304-3940(95)12105-d

Cited by 8 publications

(4 citation statements)

References 10 publications

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“…Lassa virus, Junin virus, and other hemorrhagic arenaviruses enter the brain and cause neurological symptoms that can include encephalitis, hearing loss, and tremors [41,42]. Similar to our observations in CCHFV brain infection of SGM3 humanized mice, Junin virus also infects astrocytes, and neurodegenerative reactive astrogliosis may play a role in the pathogenesis of acute and late neurological symptoms in Junin virus infection [43][44][45][46]. Furthermore, many closely related bunyaviruses, including those of the California serogroup (genus Orthobunyavirus) and Rift Valley fever virus (genus Phlebovirus) are well characterized as causing neurological symptoms in human disease, supporting the potential for more frequent neurological involvement in CCHF than currently recognized.…”

Section: Discussionsupporting

confidence: 82%

Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells as Primary Targets of Neurological Infection

Spengler

Keating

McElroy

et al. 2017

The Journal of Infectious Diseases

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Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. In the current study, we inoculated NSG-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low-passage CCHF virus strains isolated from human patients. In humanized mice, lethal disease develops, characterized by histopathological change in the liver and brain. To date, targets of neurological infection and disease have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis, and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggest a role for astrocyte dysfunction in neurological disease and identify key regions of infection in the CNS for future investigations of CCHF.

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Section: Discussionsupporting

confidence: 82%

Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells as Primary Targets of Neurological Infection

Spengler

Keating

McElroy

et al. 2017

The Journal of Infectious Diseases

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“…In our experimental model, we confirmed the presence of widespread astrocyte reaction in infected animals. In this connection, JV induction of astrocyte activation has also been described in rat brain cell cultures [Berría and Lascano, 1985] and such increased cell maturation proved concomitant with transient enhancement of both phagocytic activity [Iacono et al, 1991] and GFAP immunochemical profile [Iacono et al, 1995]. Bearing in mind that greater mortality was observed in AG-treated mice displaying lower astrocyte reactivity, as appreciated by cursory inspection, though viral infectivity titers were similar regardless of treatment, intense astrocyte activation seemed as mainly beneficial, likely by exerting supportive functions or even by restoring damaged tissues.…”

Section: Discussionmentioning

confidence: 90%

Junin virus‐induced astrocytosis is impaired by iNOS inhibition

Gómez

Yep

Schattner

et al. 2002

Journal of Medical Virology

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Because Junin virus (JV) experimental encephalitis of mice and rats is characterized by mild histopathological changes that do not seem to justify per se lethality after intracerebral infection, such a murine model seems adequate to investigate the potential role of inducible nitric oxide synthase (iNOS) as a pathogenic factor. Concomitant with a predominant astrocyte reaction, increased immunoperoxidase expression of iNOS, mitochondrial superoxide dismutase (SODm) and glutathione peroxidase (GPX) was disclosed in brain of mice infected with JV strain #44. When specific inhibition of iNOS was achieved by intraperitoneal administration of amino guanidine (AG), significantly greater mortality was observed in treated animals (70% vs. 40%), together with similar infective titers ( approximately 10(7) PFU/g) but lower astrocytosis, as shown by glial fibrillary acidic (GFAP) labeling. As regards SODm and GPX immunochemical expression in neurons, no differences were found between mice with or without AG treatment. The present results suggest that the apparent protective role of nitric oxide (NO), when synthesized by iNOS, is unrelated to reduced viral replication but rather to enhanced astrocyte activation behaving as a beneficial cell response to virus-induced CNS damage.

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“…In contrast, the marked increase in GFAP was delayed compared with iNOS expression, and there was no co-localization of viral and GFAP antigens on days 3-7 PI. In addition, the concomitant enhanced expression of GFAP mRNA rules out that this result is due to the previously described transient soluble detection fraction of GFAP following JV infection [13]. Moreover, GFAP expression was observed in the monolayer as foci that were increased both in number and intensity over time, suggesting a paracrine mechanism as the cause of such astrocyte activation.…”

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confidence: 71%