Herpes Simplex Virus

Added on - 26 Sep 2019

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Herpes simplex virus as a cause of Alzheimer’s diseaseIn the general population, Herpes Simplex Virus (HSV) is highly prevalent (more than 70% after age 50) . This virus persistslatently in the peripheral nervous system, and periodically reactivates with production of active virus. Herpes SimplexEncephalopathy (HSE) is a rare but very severe acute infection of the central nervous system. Although it has a verydifferent course from Alzheimer’s disease (AD), it leads to the occurrence of bilateral hippocampal-inner temporal lesionsresulting in profound verbal memory loss, characteristic of AD. On the basis of this hippocampal and temporal tropism ofthe virus, HSV was proposed as a candidate environmental risk factor for AD. Some studies found that HSV has beendetected in the brain of many AD patients, both by direct detection of virus DNA by polymerase chain reaction (PCR) and bythe detection of intrathecal antibodies. However, as the virus was also frequently detected in normal brains of agedindividuals, it is unlikely that HSV infection is the only cause of the disease, but it may participate in the pathogenic process.The fact that the frequency of HSV DNA positive subjects was not different between AD and control subjects and thatintrathecal IgG antibodies were detected in a similar proportion of patients with AD and elderly controls indicates thatchronic HSV infection alone is not univocally associated with AD. It has been suggested, however, that the risk ofdeveloping AD in subjects positive for HSV DNA presence in the brain who carried apolipoprotein E e4 allele (APOE-e4) wasseveral fold that of individuals possessing only one or neither of these factors. However, this finding remains controversialas it has not been confirmed by another study.Herpes simplex virus (HSV) is a neurotropic double-stranded DNA virus which includes the HSV-1 and HSV-2 subtypes. HSVis composed of an inner DNA core, a capsid , the tegument, and an outer envelope, which is a lipid membrane containingglycoproteins. HSV-1 infects 60-80% of people worldwide and causes infectious corneal blindness, the common cold soreand potentially fatal encephalitis. HSV is one of the leading infectious viral pathogens found in immunocompromised hosts,such as transplant recipients. HSV induces tissue damage including cell infiltration, perivascular inflammation and syncytialformation . HSV initially infects the epithelial cells and then enters the sensory nerve terminals. During its life cycle in thesensory nervous system, HSV travels by retrograde transport to the neuronal cell bodies in the trigeminal ganglia, and theneither enters latency or replicates. Replicated or reactivated HSV travels by anterograde transport out of the cell body tothe central nervous system in addition to the peripheral mucosal membrane.Alzheimer’s disease (AD) is a progressive neurodegenerative disease leading to the irreversible loss of neurons and the lossof intellectual abilities, including memory and cognition. According to the National Institute on Aging, AD afflicts 2.5-4.5millions Americans and 18 million people worldwide. AD is pathologically characterized by intracellular neurofibrillarytangles and extracellular senile plaques. While the pathogenesis of AD is still elusive, it is widely recognized that APP plays acentral role in the pathogenesis of AD based on the following evidence: i) amyloid-β precursor protein (APP) is theprecursor to beta-amyloid peptide (Abeta), a main constituent of senile plaques which causes cell death, synaptic defectsand memory impairment ; ii) Disruption of APP-mediated axonal transport contributes to the neurodegenerationassociated with AD ; iii) Aberrant APP phosphorylation results in Abeta production, cell stress and degeneration.RT-PCR studies reveal the existence of HSV-1 DNA in plaques of frontal and temporal cortices in post-mortem brains ofboth sporadic and familial Alzheimer’s disease. The presence of HSV-1 in the brain is considered to be a risk factor for AD inelderly people who carry the apolipoprotein E ε4 allele. Viral proteins of HSV-1 interact with many AD susceptibility genesor proteins. In addition, epidemiological study demonstrates that HSV-1 reactivation, as measured by seropositive IgM, is ahigh risk factor for AD and that HSV-1 chronic infection contributes to the progressive brain damage characteristic of AD. Amore recent similar study shows that anti-HSV IgG antibody avidity is higher in AD patients and much higher in subjectswith amnestic mild cognitive impairment (a prodromal stage of AD) than in controls, suggesting that seropositve IgG couldbe adopted as a biomarker for early diagnosis of amnestic mild cognitive impairment as well as AD. These data suggest alink between HSV infection and AD pathogenesis. There have been numerous studies focused on deciphering themechanisms behind this link.
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