Abstract
BackgroundMice 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.MethodsIn 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.ResultsInitially, 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.ConclusionsThe 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.
Highlights
Mice infected with HSV-1 can develop lethal encephalitis or virus induced Central nervous system (CNS) demyelination
In BL/6 mice, HSV-1 DNA and antigen positive cells are restricted to the BST In BL/6 mice infected with HSV-1 strain 2 via the oral mucosa, the spread of infectious virus is restricted to the BST [37] and CNS demyelinating lesions do not occur [33]
BALB/c mice infected with strains McKrae or KOS [38,39,40] or BL/6 mice infected with strain McRae [40] do not develop CNS demyelination but macrophage depleted BALB/c and BL/6 mice, infected with strain KOS or McKrae respectively, do develop lesions throughout the CNS [40]
Summary
Mice infected with HSV-1 can develop lethal encephalitis or virus induced CNS demyelination. HSV-1 is a common infection in developed countries where rates of seropositivity usually exceed 50% [1,2] In both humans and experimental animals, primary infection of the skin or mucosa results in the local replication. Mice infected with HSV-1 can develop lethal encephalitis with resistance to mortality being mouse strain dependent [14,15]. HSV-1 can induce CNS demyelination in mice with the nature of the demyelinating lesions reported to be dependent on virus strain [24,25,26,27,28,29,30,31], route of infection [32], and mouse strain [33,34]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
