Multiple sclerosis
(MS) is an inflammatory, autoimmune disease of the central nervous
system. The cause of MS is still unknown but epidemiological and
immunological studies have implicated Epstein-Barr virus (EBV), which
infects B cells, as a possible aetiological agent involved in disease. Of
particular interest is EBV latent membrane protein 2A (LMP2A) because
previous studies have demonstrated that LMP2A enhances the expansion and
differentiation of B cells upon antigen stimulation, revealing a
potential contribution of this protein in autoimmunity. Since B cells
are thought to contribute to MS, we examined the role of LMP2A in the
animal model experimental autoimmune encephalomyelitis (EAE). In this
model, transgenic mice in which B cells express LMP2A show increased
severity and incidence of disease. This difference was not due to
lymphocyte recruitment into the CNS or differences in T cell activation,
rather, we show that LMP2A enhances antigen presentation function
This report in scientific methods reports that a protein made by EBV augments neurological attack caused by enhancement of antigen presentation by B cells. However, the evidence that B cells are that important in early stages of EAE is rather lacking. Indeed you can get normal EAE in the complete absence of B cells as shown previously , although it has been shown that B cell activity can augment T cell-mediated autoimmunity.
This study reports on some odd findings and it
would be a very surprsing that increases severity of disease are
not associated with increased recruitment into the CNS. So when we look at the data, first thing to say they report using tests that are not correct for the data) and using the "smack you in the eye test", there looks to be no real difference. On closer look at the data they compare a mean
score on 2.7 verses 2.3 respectively , however with an incidence of 92% and 79%. This
means the scores of the affected animals are 2.9 and 2.9. If the clinical
scores are compared like for like you would not expect any
difference. They see a small difference but is it simply skewed by the
fact that less animals got disease in the transgenic than wild type-normal mouse. Abit of a Shania. Best stop there before I say too much.
Casiraghi C et al. Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis. PLoS Pathog. 2012 May;8(5):e1002715.
Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis
(MS), yet EBV's role in MS remains elusive. We utilized murine gamma
herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how
infection by a virus like EBV could enhance CNS autoimmunity. Mice
latently infected with γHV-68 developed more severe EAE including
heightened paralysis and mortality. Similar to MS, γHV-68EAE mice
developed lesions composed of CD4 and CD8 T cells, macrophages and loss
of myelin in the brain and spinal cord. Further, T cells from the CNS of
γHV-68 EAE mice were primarily Th1, producing heightened levels of
IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17
response was observed in uninfected EAE mice. Clearly, γHV-68 latency
polarizes the adaptive immune response, directs a heightened CNS
pathology following EAE induction reminiscent of human MS and portrays a
novel mechanism by which EBV likely influences MS and other autoimmune
diseases.
life cycle of gamma HV-68
This report talks about mice infected with a virus gamma-HV-68.
It is suggested that this is a mouse equivalent of EBV, but does it
cause lymphoma, B cell immortalisation etc, etc. However according to
Wikipaedia, "MHV-68 is more closely related to the Kaposi's Sarcoma-associated herpesvirus (KSHV) than it is to the Epstein-Barr virus" If so the argument falls apart. So not so good EAE becomes good EAE when there is a viral infection. This latent virus does not re-activate and infect the CNS during EAE.
Just
so you know there have been studies on viruses and EAE for many years
including the first description of the use of the PL mouse strain. Unfortunately I can remember this paper from when it first came out...I am an old f**t :-)
Cross
AH, McCarron R, McFarlin DE, Raine CS. Adoptively transferred acute and
chronic relapsing autoimmune encephalomyelitis in the PL/J mouse and
observations on altered pathology by intercurrent virus infection .Lab Invest. 1987;57(5):499-512.
PL/J
mice developed chronic relapsing experimental allergic
encephalomyelitis (EAE) after receiving syngeneic guinea pig basic
protein (GPBP)-immune lymph node cells or spleen cells which were
cultured in the presence of GPBP or the encephalitogenic N-terminal
peptide of GPBP. The presence of CD4+ cells and in vitro proliferation
in response to GPBP are required for the successful transfer.
Pathologically, adoptively-(T cell) transferred EAE in the virus-free PL/J
strain was characterized by an infiltration in the central nervous
system by small lymphocytes, followed by the appearance of macrophages,
and subsequently by primary demyelination. These findings were similar
to those previously observed in chronic relapsing EAE in SJL/J mice.
However, in some experiments pathologic examination of the spinal cord
showed large demyelinating lesions which were necrotic and infiltrated
with eosinophilic polymorphonuclear leucocytes. Sera from mice with this
pathology contained antibodies to murine hepatitis virus
and extensive search identified a few areas of coronavirus replication.
The pathology of autoimmune mediated demyelination may be altered in
the presence of coronavirus infection but the clinical pattern of EAE
expression did not differ between virus-free and coronavirus-infected mice.
