What is the clinical evidence from this study?

Study design: Other. Population: Herpes simplex virus type 1 (HSV-1) infection of the central nervous system. Intervention: HSV-1 (strain 2) infection vs. Mock infected controls / resistant mouse strains. Primary outcome: Development, number, and size of 'focal' areas of viral antigen positive cells and demyelinating lesions.

January 1, 2012Open Access

The effect of mouse strain on herpes simplex virus type 1 (HSV-1) infection of the central nervous system (CNS)

LKLorne F. KastrukoffUniversity of British Columbia ALAllen S. LauUniversity of British Columbia ÉTÉva ThomasBC Cancer Agency

Key Result

Susceptible mouse strains infected with HSV-1 develop CNS demyelination associated with focal areas of viral antigen, whereas resistant strains restrict the virus to the brainstem without demyelination.

Structured PICO

Population

Female inbred mice of five different strains infected with HSV-1 via the oral mucosa to study the development of CNS demyelination over 30 days.

Intervention

Infection with a sub-lethal dose of HSV-1 strain 2 via the oral mucosa

Comparator

Comparison between different mouse strains (susceptible SJL/J, A/J, PL/J vs moderately resistant BALB/c vs resistant BL/6)

Outcome

Relationship between virus and the development of lesions during the early stage (< 24 days PI) of demyelinationsurrogate

The extent of CNS demyelination following oral HSV-1 infection in mice is strain-dependent and correlates with the development of focal areas of virus-infected cells in the brain.

Limitations

Animal model findings may not fully translate to human disease
The specific immune mechanisms mediating the clearance of virus have not yet been fully defined

Abstract

BACKGROUND: Mice infected with HSV-1 can develop lethal encephalitis or virus induced CNS demyelination. Multiple factors affect outcome including route of infection, virus and mouse strain. When infected with a sub-lethal dose of HSV-1 strain 2 via the oral mucosa, susceptible SJL/J, A/J, and PL/J mice develop demyelinating lesions throughout the brain. In contrast, lesions are restricted to the brainstem (BST) in moderately resistant BALB/c mice and are absent in resistant BL/6 mice. The reasons for the strain differences are unknown. METHODS: In this study, we combine histology, immunohistochemistry, and in-situ hybridization to investigate the relationship between virus and the development of lesions during the early stage (< 24 days PI) of demyelination in different strains of mice. RESULTS: Initially, viral DNA and antigen positive cells appear sequentially in non-contiguous areas throughout the brains of BALB/c, SJL/J, A/J, and PL/J mice but are restricted to an area of the BST of BL/6 mice. In SJL/J, A/J, and PL/J mice, this is followed by the development of 'focal' areas of virus infected neuronal and non-neuronal cells throughout the brain. The 'focal' areas follow a hierarchical order and co-localize with developing demyelinating lesions. When antigen is cleared, viral DNA positive cells can remain in areas of demyelination; consistent with a latent infection. In contrast, 'focal' areas are restricted to the BST of BALB/c mice and do not occur in BL/6 mice. CONCLUSIONS: The results of this study indicate that susceptible mouse strains, infected with HSV-1 via the oral mucosa, develop CNS demyelination during the first 24 days PI in several stages. These include: the initial spread of virus and infection of cells in non-contiguous areas throughout the brain, the development of 'focal' areas of virus infected neuronal and non-neuronal cells, the co-localization of 'focal' areas with developing demyelinating lesions, and latent infection in a number of the lesions. In contrast, the limited demyelination that develops in BALB/c and the lack of demyelination in BL/6 mice correlates with the limited or lack of 'focal' areas of virus infected neuronal and non-neuronal cells in these two strains.

Perguntar à IA

Bookmark

View Full Paper