Multiple sclerosis patients usually have high levels of antibodies indicating past infectious from several common viruses, but a live virus associated with multiple sclerosis has not been consistently observed.
Therefore, to date, no specific virus has been confirmed as a causative agent for multiple sclerosis. The authors explained that it's possible that multiple viruses could influence susceptibility to multiple sclerosis. The ability of any particular virus to contribute to the disease could depend on an individual's own repertoire of other predisposing genes, exposure to other predisposing environmental factors, and the random chance that T cells had been generated that recognize a myelin protein and a pathogen.
Receptors on T cells are randomly generated during their development. This observation helps explain why multiple sclerosis is partly a matter of chance. Some people with a genetic predisposition and environmental exposure develop the disease, while others with similar genetic predisposition and environmental exposure do not. It's uncertain how common these dual-receptor T cells are, according to the researchers, although there are reports that up to one-third of human T cells express dual receptors.
Goverman and her group plan to test samples from multiple sclerosis patients and see how many have dual-receptor T-cells. Materials provided by University of Washington. Note: Content may be edited for style and length.
Science News. White blood cells with receptors for both virus and nerve proteins may assault nerves after fighting an infection advertisement. Story Source: Materials provided by University of Washington. Nature Immunology , ; DOI: ScienceDaily, 14 June University of Washington. Virus infection may trigger unusual immune cells to attack nerves in multiple sclerosis. Retrieved September 24, from www. Diabetes devastates nerve cells, which can lead to poor circulation, They found that this molecule, called VGF nerve growth factor, helps Multiple sclerosis is a Below are relevant articles that may interest you.
ScienceDaily shares links with scholarly publications in the TrendMD network and earns revenue from third-party advertisers, where indicated. On the Keto Diet? Ditch the Cheat Day Boy or Girl? Living Well. Studies of viruses from several families show that the normal mode of viral release is blocked or altered in neurons. For example, in the persistent infection caused by the murine pathogen LCMV, viral RNA is readily detected in neurons by in situ hybridization [ 39 ], but electron microscopic EM examination does not reveal budding viral particles [ 40 ], which are readily visible in susceptible fibroblasts [ 41 ].
In studies with MV, a similar cell type-specific difference was observed. In susceptible fibroblasts, MV infection is highly productive and cytolytic; viral spread occurs by the production of extracellular progeny and by the fusion of infected cells with adjacent uninfected cells. In neurons, MV spread occurs in the absence of extracellular virus, syncytia formation, or neuronal lysis. Decreased virus production correlates with an inability of MV to form buds at the neuronal plasma membrane [ 42 ].
MV transmission throughout these neuron cultures is not inhibited by neutralizing antibodies, paralleling rabies studies in which neutralizing antibodies are less effective in preventing spread in neurons than in nonneuronal cells [ 43 ]. Together, these data indicate a novel mechanism of MV transmission in neurons [ 42 , 44 ]. EM studies of neuronal infection with wild type MV strains revealed the presence of viral ribonucleoproteins RNPs at the neuronal synapse [ 42 , 45 ], supporting earlier observations by researchers who used mouse-adapted strains [ 46 , 47 ].
Pasick et al. Thus, while neurons may place restrictions on viral replication to limit cytopathicity, viruses may in turn encode proteins that facilitate neuronal transport.
The Mechanisms of Neuronal Damage in Virus Infections of the Nervous System
The lack of requirement for CD46 may mean that the hemagglutinin protein that interacts with the cellular receptor may also be dispensable for neuronal infection, although for other RNA viruses that spread via the synapse, such as rabies, a requirement for the viral surface proteins was noted [ 49 ]. Whether MV utilizes an alternative receptor at the synapse or sequesters the transsynaptic machinery to be transported across the synapse to infect the postsynaptic neuron is not yet resolved.
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While promotion of transsynaptic viral spread may prevent direct lysis of neurons, such an altered mode of transmission may benefit the virus as well. For example, viruses that spread transsynaptically and do not release viral particles may be invisible to the humoral immune response [ 50 ].
Age dependence and neuronal maturity Often the outcome of infection with neurotropic RNA viruses differs depending on the age of the infected host e. The opposite occurs in NSE-CD46 transgenic mice after MV infection: Infection of neonates is lethal but infection of adults results in viral clearance [ 18 , 19 ].
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In both cases, the differential outcome of infection is due to immunologic differences: In the LCMV-infected adult mice, for example, death is due to a vigorous CTL response that results in choriomeningitis, edema, and mortality [ 41 ]. However, age-related differences in response to viral infection may also be due to the differentiated status of the infected neuron [ 51 ].
For example, infection of mouse neurons with the A7 74 strain of Semliki Forest virus causes mortality in neonatal animals but not in adults due to the inability of virus to bud from adult neurons [ 52 , 53 ]. While the exact nature of this abortive infection remains under study, the metabolism of rapidly dividing neurons differs substantially from that of fully differentiated nondividing neurons. Differences such as axonogenesis and myelination likely have a significant impact on the mechanics of viral replication.
Although we propose that neurons may be more able to deploy antiviral tactics than generally believed, we do not suggest that viral infections of neurons are not a significant public health problem. Even though infections may be held off from inducing immediate damage, many chronic CNS infections eventually result in some form of CNS disease, months or even years after exposure. Such CNS damage can occur as a consequence of neuronal dysfunction, blood-brain barrier damage, glial activation, immune cell infiltration, or some combination [ 8 ].
In most cases, it is not known whether these lesions develop slowly after CNS infection or are rapidly manifested after a prolonged period of quiescent infection. Human diseases associated with chronic infection of the brain include subacute sclerosing panencephalitis SSPE following acute MV infection, the spongiform encephalopathies caused by some lentiviruses, chronic neurodegeneration after Borna disease virus BDV infection, postinfluenza encephalitis, mumps meningoencephalitis, and CNS neoplasms possibly resulting from the human polyomaviruses JC and BK [ 8 ].
In addition to these serious but relatively rare disorders, there is considerable debate in the literature concerning the possible association of viruses with CNS disorders of unknown etiology. These include highly controversial reports linking BDV with schizophrenia [ 54 ], echoviruses with amyotrophic lateral sclerosis [ 55 ], a number of viruses with demyelinating diseases [ 8 ], and inoculation of the measles-mumps-rubella vaccine with autism [ 56 ].
While a formal association between these diseases and viral infection awaits further study, it is certain that we do not yet know the degree to which the CNS can be influenced by persistent infections. Even when a viral etiology is suspected, the basis for neurologic impairment may not be apparent. These deficits correlate with neurochemical alterations, including transcriptional suppression of the neurotransmitter somatostatin [ 59 ] and the synaptic structural protein GAP [ 60 ].
Thus, while these mice survive a persisting LCMV infection with little overt neuropathology, the influence of viral infection on cellular gene expression may compromise the functional capacity of infected neurons.
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Chronic infections may also cause neurologic impairment indirectly. While the precise basis of this indirect neuropathology is unresolved, it seems likely that virus-mediated impairment of microglia which play an important supportive role for neurons could lead to a depletion of neurotropic factors or an accumulation of neurotoxic factors [ 61 ].
While evidence of the AIDS dementia complex does not usually appear until the terminal stages of the disease, CNS infection often occurs soon after seroconversion [ 8 ]. Thus, either infection and the onset of pathology occur simultaneously and the apparent delay between infection and clinical symptoms reflects the requirement for a threshold level of CNS damage or some change occurs months to years after quiescent infection and results in rapid onset of neuronal destruction.
In this scenario, restrictions imposed by the host cell on virus production or cytopathicity may be bypassed by the spontaneous generation of neurovirulent variants that could initiate a rapid disease course. Viral RNA isolated from patients who died of MV-induced SSPE consistently contained biased hypermutations in the envelope-associated genes, matrix, fusion and hemagglutinin [ 63 , 64 ], which may be associated with induction of CNS disease.
These data support the hypothesis that cytopathic variants may arise in patients who develop SSPE, although it is not known whether these defective virions are involved in MV-associated neuropathology. Even though our appreciation of the interplay between viruses and neurons is quite recent, a substantial body of evidence suggests that viral infections of neurons differ substantially from infection of nonneuronal cells. Neurons possess strategies to curtail viral replication, rapidly recruit the antiviral immune response to the brain parenchyma, and exploit noncytolytic effector mechanisms of viral clearance.
Further efforts to understand how the neuronal microenvironment alters the virus life cycle will affect our understanding of both viruses and neurons. Moreover, the presence of many subpopulations of CNS neurons implies that neurons in different regions of the brain may respond to viral infections in unique ways.
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A better understanding of the complex interaction between pathogens and the immune response in the brain will contribute to the development of therapies to prevent or reverse viral infections of neurons and the diseases they cause. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In.
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Mechanisms of Virus-Induced Neuronal Damage and the Clearance of Viruses from the CNS
Volume Article Contents. Background: Virus Particle versus Infectious Particle. Intraneuronal Restrictions on Viral Replication and Spread. Reprints or correspondence: Dr. Glenn F. Oxford Academic. Google Scholar. John K. Cite Citation.
Pathways of Infection
Permissions Icon Permissions. Abstract Neurons of the mammalian central nervous system CNS are an essential and largely nonrenewable cell population.
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The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease.