Lopatko Lindman et al. Linard et al. A novel genetic approach was reported by Pandey et al. GM17 has an increased affinity for a decoy receptor of HSV1, a complex of two glycoproteins, gE-gI on the surface of the virion and infected cells, that binds the Fc region of host IgG and is implicated in cell-to-cell spread of virus. Other evidence supporting the possibility that HSV1-specific antibodies have a protective effect against AD development includes the fact that AD incidence increases with age-dependent blood-brain barrier BBB injuries, although detected in normal brain, are more pronounced in mild cognitive impairment MCI subjects [ 63 , 64 ], so a relatively high concentration of HSV1-specific antibody could limit viral reactivation in brain regions where the BBB is disrupted.
Montagne et al. The efficacy of humoral responses is also determined by antibody avidity. Whether or how this risk and this symptom interact and whether and how infection is involved are major questions. In fact, two interesting studies on cognition and infectious agents and two on APOE and cognition have recently been published.
A very intriguing one is that of Zhao et al. IB was assessed by a quantitative weighted index of exposure to common pathogens associated with vascular risk, infectious burden index IBI , and by serology for individual infections. They had previously found an association between an IBI, a composite serologic measure of exposure to common pathogens linked to stroke risk, and poor cognitive performance on global cognitive measures.
Subsequently, using detailed full neuropsychological testing, they found an association between IB and the executive function domain, and also decline in memory over time. IgG titres were used for all the pathogens except C. Cognition was assessed by completion of the MMSE at baseline, and by a full neuropsychological test battery, comprising cognitive domains of memory, processing speed, language, and executive function, after a median follow-up of approximately 6 years. Episodic memory impairment is one of the first preclinical signs of AD, and is strongly associated with increased age-related AD risk, although its course varies greatly among individuals.
The study of Gharbi-Meliani et al. The survey investigated subjects in the Whitehall II Study, an ongoing cohort study of persons originally employed by the British Civil Service, all Caucasian. However, as they said, explanations or deductions are limited, because most research on APOE had been made on subjects of age 65 years or older, who have been followed for less than 10 years. The authors concluded that their longitudinal study produced two main findings.
These results provide support for the antagonistic pleiotropic hypothesis. They too were probably unaware, like Zhao et al.
Murphy et al. The authors measured serum IgG antibodies to HSV1 collected between and , and changes in cognitive performance during 2 consecutive examinations 6. Controls were seronegative people. HSV1 seropositivity was associated with decline in global cognition, as well as in separate cognitive domains.
They therefore suggested that HSV1 is associated only with subtle cognitive disturbances but not with greater cognitive disorders that result in dementia. Further, their comparison with the Taiwanese study of Tzeng et al. Major disruptions to cellular processes that are thought to be involved in AD and their possible causes include oxidative stress OS , which has been strongly implicated in AD pathology, and HSV1, which is known to cause such stress.
AD brains have high levels of polyunsaturated fatty acids, the substrate for lipid peroxidation, also a high rate of oxygen usage, low level of antioxidants and they show increased levels of oxidative stress markers, such as various protein derivatives, and lipid oxidation products. Herpes simplex encephalitis the rare but very serious acute HSV1 infection of brain increases production of reactive oxygen and nitro species, which contributes to oxidative stress also, HSV1-infected neural cell cultures produce increased levels of reactive oxygen species ROS , resulting in neuronal oxidative damage including lipid peroxidation.
Recently, Protto et al. Protto et al. They found that the reactivations cause oxidative modification in lipids and proteins in the cortex, most of the proteins being involved in cellular processes such as energy metabolism, protein folding, degradation process, and cell structure—pathways linked to AD onset and progression.
They concluded that repeated reactivation in brain might contribute to neurodegeneration through oxidative damage such as accumulation of misfolded proteins, perturbation of the cytoskeleton network and of clearance mechanisms for oxidised proteins and DNA, leading to cell translation machinery being used for synthesising viral instead of cell proteins. The likelihood that HSV1 effects on clearance of damaged proteins and on autophagy might relate to AD was proposed in [ 73 ].
Subsequently, details of the impairment of clearance mechanisms of the lysosome system by HSV1 via oxidative stress have been reported in many studies, most recently by Kristen et al. They found in a cell model of AD that HSV1 and OS increased lysosome load, reduced activity of lysosomal hydrolases, affected cathepsin maturation, and inhibited endocytosis-mediated degradation of the epidermal growth factor receptor, indicating impairment of the lysosome system.
They drew a similar conclusion from functional genomic analysis. Duarte et al. They commented that although apoptosis is considered to be a result of neurodegeneration, alterations in signalling pathways related to apoptosis have been widely implicated in neurodegenerative diseases such as AD; they could be caused by HSV1 modulation of neuronal apoptosis during infection: host cells use apoptosis during viral infection in order to eliminate the virus and to combat this, HSV1 modulates apoptosis-related pathways at multiple stages after infection of neurons, during both acute and latent infection, leading to either the induction or the blockage of apoptosis.
The virus can thus manipulate neuronal survival and its own persistence. However, Doll et al. The involvement of mitochondrial damage in AD was discussed by Reddy et al.
Recently, Pradeepkiran and Reddy [ 78 ] described impairment of mitophagy, a process whereby damaged mitochondria are selectively removed from cells, so that progressive accumulation of defective organelles and damaged mitochondria occurs. As to HSV1 and mitophagy, only one study has investigated effects of the virus on mitophagy: Waisner and Kalamvoki [ 79 ] found that HSV1 evades the host mechanisms of autophagy and mitophagy, which are defence mechanisms against pathogens, through the downregulation of the autophagy adaptor protein, sequestosome, and of the mitophagy adaptor, optineurin, via the HSV1 protein, ICP0.
Details of the precise mechanisms whereby HSV1 operates over the years to cause the development of the disease are yet to be discovered: a challenge bearing in mind the bewildering array of effects of the virus and the very unfortunate inability at present to detect it even when reactivated in the brain in life. An alternative to VCV would be usage of a helicase primase inhibitor: interestingly, a study of a new such inhibitor, IM, which provides in animals sufficient brain exposure and a potentially superior dose regimen of once daily or even once weekly rather than the usual twice daily is in press [ 80 ].
Equally, or even more exciting would be a trial to investigate the apparent protective effects of vaccination, particularly of BCG, against the development of dementia, and a trial treating symptomatic sufferers of HSV1 with antiviral agents in their middle years, well before any signs of dementia are detectable.
Prevention of dementia would a truly marvellous outcome. I thank the Advantage Foundation for financial support. National Center for Biotechnology Information , U. Journal List Vaccines Basel v. Vaccines Basel. Published online Jun Ruth F. Author information Article notes Copyright and License information Disclaimer. Received May 18; Accepted Jun This article has been cited by other articles in PMC. Open in a separate window. Figure 1. Effect of Treatment with Antivirals for HSV and VZV Infection prior to Onset of Dementia Some very surprising but potentially important results, if verified, dealing with the consequence of herpesvirus reactivation have been reported.
Vaccination Protection against Risk of AD and of HSV1 Reactivation Whichever viruses are involved in AD, one would assume that to prevent their action, specific vaccines would be needed against each one.
Anti-HSV Serum Antibodies and Risk of AD As mentioned earlier, in the section on effect of treatment with antivirals for HSV and VZV infection prior to dementia onset, there have been a number of studies investigating the presence, level, and avidity relative strength of antibody-binding to antigens of antibodies to HSV1, specifically immunoglobulin G IgG and immunoglobulin M IgM ; the former denotes presence of HSV1 in the periphery, and the latter its reactivation there.
Acknowledgments I thank the Advantage Foundation for financial support. Funding This research was funded by the Advantage Foundation. Institutional Review Board Statement Not applicable. Informed Consent Statement Not applicable.
Conflicts of Interest The author declares no conflict of interest. References 1. Itzhaki R. Abrahamson E. Cairns D. Wozniak M. Choi S. Cummings J. Xiao S. Wang W. The antiviral activities and mechanisms of marine polysaccharides: An overview. Harden E. Virucidal activity of polysaccharide extracts from four algal species against herpes simplex virus.
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Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus. Gharbi-Meliani A. Please note: A herpes blood test can help determine if you have herpes infection. It cannot tell you who gave you the infection or when you got the infection. If you are sexually active, you can do the following things to lower your chances of getting genital herpes:.
Be aware that not all herpes sores occur in areas that a condom can cover. Also, the skin can release the virus shed from areas that do not have a visible herpes sore. For these reasons, condoms may not fully protect you from getting herpes. There is no cure for genital herpes. However, there are medicines that can prevent or shorten outbreaks.
A daily anti-herpes medicine can make it less likely to pass the infection on to your sex partner s. Genital herpes can cause painful genital sores and can be severe in people with suppressed immune systems. If you touch your sores or fluids from the sores, you may transfer herpes to another body part like your eyes.
Do not touch the sores or fluids to avoid spreading herpes to another part of your body. If you do touch the sores or fluids, quickly wash your hands thoroughly to help avoid spreading the infection. If you are pregnant, there can be problems for you and your unborn fetus, or newborn baby.
How could genital herpes affect my baby? If you are pregnant and have genital herpes, prenatal care visits are very important. Some research suggest that a genital herpes infection may lead to miscarriage or make it more likely to deliver your baby too early.
You can pass herpes to your unborn child before birth, but it more commonly passes during delivery. This can lead to a deadly infection in your baby called neonatal herpes. It is important that you avoid getting genital herpes during pregnancy. Tell your healthcare provider if you have ever had a genital herpes diagnosis or symptoms.
Also tell them about any possible exposure to genital herpes. If you have genital herpes, you may need to take anti-herpes medicine towards the end of your pregnancy. This medicine may reduce your risk of having signs or symptoms of genital herpes when you deliver. At the time of delivery, your healthcare provider should carefully examine you for herpes sores.
If you have herpes, you should talk to your sex partner s about their risk. Using condoms may help lower this risk but it will not get rid of the risk completely. Having sores or other symptoms of herpes can increase your risk of spreading the disease. Even if you do not have any symptoms, you can still infect your sex partners. You may have concerns about how genital herpes will impact your health, sex life, and relationships. While herpes is not curable, it is important to know that it is manageable with medicine.
Daily suppressive therapy i. Talk to a healthcare provider about your concerns and treatment options. A genital herpes diagnosis may affect how you will feel about current or future sexual relationships. Knowing how to talk to sexual partners about STDs external icon is important. Herpes infection can cause sores or breaks in the skin or lining of the mouth, vagina, and rectum.
This provides a way for HIV to enter the body. Even without visible sores, herpes increases the number of immune cells in the lining of the genitals.
HIV targets immune cells for entry into the body. Box Rockville, MD E-mail: npin-info cdc. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Genital Herpes. Section Navigation. Facebook Twitter LinkedIn Syndicate. Minus Related Pages. People who are sexually active can get genital herpes, a common sexually transmitted disease STD. What is genital herpes? What is oral herpes? Is there a link between genital herpes and oral herpes?
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