AD and HSV-1 Pathobiology

Individuals with frequent recurrent herpes labialis carried the naturally occurring ε4 allele of the apolipoprotein E (ApoE) gene more often than HSV-1-seropositive individuals who did not experience recurrences of the disease. Interestingly, a similar relationship has been reported for ApoE ε4 carriage and risk of Alzheimer’s disease (AD) development.

The presence of the ε4 allele and HSV-1 disease states has been studied, and these studies have supported the conclusion that the ε4 allele is a risk factor for both HSV-1 recurrence and AD. Several recent reports indicate, however, that the ε4 allele is not a predisposing factor for herpes simplex encephalitis or keratitis, but a potential role for other ApoE isoforms was suggested.

Similar to HSV-1 central nervous system (CNS) infection, the presence of the ApoE ε4 allele is neither sufficient nor essential for AD development, since many octogenarians who carry ε4 genotypes do not show AD pathologies. This lack of causation again supports associations with other unidentified genetic factors or environmental risk factors such as infectious agents.

Clearly, more work is needed to elucidate the role of ApoE in both AD and HSV-1 pathobiology. The indicating that ApoE plays a potential role in HSV-1 disease makes the combination an interesting area of AD research. Apolipoprotein E, a 299-amino acid glycoprotein, may affect HSV-1 pathogenesis in a number of ways, as suggested by several of its ascribed functions.

ApoE plays important roles in the physiology of neural tissue, including control of neurite outgrowth and branching, microtubule depolymerization, adhesion to basal membrane components, immunomodulation and potentiation of the activity of cilliary neurotrophic factor. Interestingly, ApoE proteins have been shown to be components of AD neurofibrillary tangles and to bind to the beta-amyloid peptides that are involved in fibril formation.

The human ApoE gene is polymorphic with three common allelic forms designated ε2, ε3 and ε4, which encode E2, E3 and E4 protein isoforms, respectively. The E2 and E4 isoforms differ from E3 by only a single amino acid substitution at residue 158 or 112, respectively. In many assays, E2 and E3 produce similar effects that vary only in amplitude whereas the presence of E4 often leads to an altered outcome.

In primary neuronal cultures, the presence of E2 or E3 enhances neurite outgrowth and branching. The addition of E4 to cultures, however, significantly reduces both the outgrowth of neurites and branching. In addition to AD, pathological conditions, including pugilistic dementia, HIV-associated dementia, cerebral palsy and cardiovascular disease, have been associated with ε4 genotypes in an allelic dosage-dependent manner.

It has been suggested that HSV-1 infections occur in subpopulations of neurons, and that such neurons have a distinct environment predisposed to reactivatable, latent HSV-1 infections. The E4 isoform may predispose more neurons to becoming infected during primary infection. Also, the E4 isoform may enhance HSV-1 reactivation of latent infections leading to more frequent CNS damage that might trigger the development of neurological pathologies.

If E4 predisposes humans to such infections, one would anticipate higher frequencies of recurrent disease in individuals with an ε4 genotype. Increased cumulative tissue damage and inflammation would also be predicted and may be a trigger for the development of neurological pathologies. Similarly, E4’s altered activities in neurons compared with E2 and E3 may result in a reduced ability to resolve neuronal membrane injuries or stresses that could enhance the induction of HSV-1 reactivation.

Although not the sole causative agent, HSV-1 has been the most clearly established pathogen to be associated with AD development to date. The understanding of the relationship between HSV-1 infection, host genetics and the development of AD may lead to new strategies to prevent and treat AD. Cure of herpes becomes necessary especially for those caused by HSV-1.

OutbreakBalm-Rx is composed of naturally occurring high intensity antiviral extracts which have a lethal effect against herpes simplex viruses 1 and 2 upon exposure. This treatment provides maximum and rapid penetration of antiviral agents into cell membranes without damaging human cells.

Topical application of this antiviral treatment inhibits and kills the herpes virus, making it an important and versatile remedy for home use in the fight against herpes. It therefore comes as no surprise that application of this product during prodrome, the tingling before an outbreak, can prevent herpes blisters forming, aborting the pending flare up altogether.

The anti HSV properties in OutbreakBalm-Rx are highly pronounced and well documented. They quantifiably destroy the herpes virus, thus characterizing OutbreakBalm-Rx as a potent anti herpes agent. To learn more, please go to http://www.naturespharma.org.