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Herpes Simplex Virus and Neurodegeneration: Evidence (Herpes Simplex Virus…
Herpes Simplex Virus and Neurodegeneration: Evidence
Herpes Simplex Virus Type 1 (HSV)
Affects the CNS
Infects
epithelial cells of oral and nasal mucosa
Replicates
Enters sensory neurons and establishes a
latent infection
Causes sores
Contagious
Skin-to-skin contact transmission
No cure
HSV and Alzheimer's Disease (AD)
HSV DNA found in many brains of elderly people in its
latent
forms
Located within amyloid plaques in AD brains
Reactivates in brain causing infection which leads to severe damage and cell death
Could reactivation cause gradual, localized damage which could lead to development of AD?
HSV hijacks cell machinery and binds to proteins that regulate apoptosis
Apoptosis
is important in degradation of amyloid proteins
Lack of apoptosis leads to accumulation of beta amyloid and tau
Epidemiological
HSE affects the same brains involved in AD in humans and rodents
Other infectious agents can reactivate and replicate in the CNS
Genetic
Genes that mediate viral entry into neurons and defense mechanism could be working mechanistically to cause AD
HSV infection could increase risk of AD in APOE-E4 carriers
Immunological
Anti-HSV IgM associated with reactivation of HSV
Anti-HSV IgG demonstrates only in persons infected with HSV
Letenneur et al. (2008): IgM-positive more likely to develop dementia
High IgM levels --> low plasma levels of AB1-40 and AB1-42-->
high amyloid beta in brain cells
virus reactivation --> changes in APP process --> AD
Molecular evidence
HSV affects APP processing
HSV contributes to production of APP cleavages/fragments which have neurotoxic effects that lead to AD
HSV can bind to neuronal membranes which leads to
neuronal degeneration
HSV can cause Ca-mediated APP phosphorylation