Herpesviruses: A Modern View of Persistence, Diagnosis and Treatment
Introduction
Current state of knowledge (2018–2026)
Herpesviruses is not a single disease, but a whole family of viruses that accompany a person practically all his life. WHO notes that most adults are infected with herpesviruses (HSV-1, HSV-2, VZV/HHV-3, EBV/HHV-4, CMV/HHV-5, HHV-6, HHV-7), and often several types at the same time.
Infection occurs mainly in childhood or adolescence, but most people are not even aware of their presence until they begin to affect their well-being.
Thus, the current understanding of herpesviruses is based on the fact that they are capable of latent life-long carriage, complex interaction with immunity and can provoke systemic consequences.
In the 2020s, researchers found that they affect not only the usual blisters or sores, but can also be associated with other diseases. For example, the Epstein-Barr virus has been shown to be very closely related to multiple sclerosis, and the herpes simplex virus (HSV-1) can accelerate Alzheimer’s disease (by affecting amyloid pathology in the brain).
Only in the last five years has information emerged about the complex mechanisms by which these viruses hide from the immune system.
Data has been accumulated on how exactly herpesviruses infect cells and remain in the body. For example, scientists have discovered that herpesviruses can change the surface of cells and block antibodies, which helps them avoid the immune response.
A separate direction of modern research concerns the possible connection between herpes virus infections and the risk of dementia.
Some recent observational studies show that in people with clinically significant (partially reactivated) infections, the use of antiherpetic drugs was associated with a lower risk of dementia in the future. However, this does not mean that such drugs can already be recommended for the prevention of Alzheimer’s disease or other neurodegenerative conditions. Currently, this is a promising scientific direction that needs to be confirmed in randomized clinical trials.
Several large observational studies and meta-analyses have shown that people with clinically diagnosed HSV or VZV infections who received antiherpetic drugs had a lower risk of subsequent dementia compared with untreated patients. For example, a 2026 meta-analysis of 14 cohort studies and more than 10 million people aged 50 and over found an association between the use of antiherpetic drugs and a lower risk of dementia; the effect was most marked in severe alpha-herpesvirus infections, particularly HSV and VZV. However, these data do not prove that acyclovir, valacyclovir, famciclovir, ganciclovir or valganciclovir can be used as a standard prophylaxis of dementia. This requires randomized clinical trials.
The report discusses the main findings, phases of infection, complications, and new approaches to the diagnosis and treatment of herpes infections.
Research has also proven that EBV infection almost always precedes the development of multiple sclerosis. In particular, for 2018–2026, attention has increased to the role of herpes in diseases of the brain and immune system. These new facts change the previous ideas that the herpes virus is just a “simple herpes virus” – now it is known that it can have multifaceted health consequences.
The role of herpesviruses in chronic diseases and immune regulation
This decade has seen new insights into how herpesviruses are linked to chronic disease. In particular, early EBV infection in adolescence has been shown to increase the chances of developing multiple sclerosis in adulthood. There are suspicions that herpesviruses also accelerate the aging of the brain, associated with the formation of pathological amyloid in Alzheimer’s disease. Regarding immunity, scientists note that herpesviruses actively avoid immune reactions – their proteins are rarely found in the cell, and special viral mechanisms extinguish the attack of antibodies and the cellular immune response. Another proven fact: some herpesviruses cause cancer. For example, EBV causes certain types of lymphoma and nasopharyngeal carcinoma, and KSHV (HHV-8) causes Kaposi’s sarcoma. Other herpesviruses (eg, HHV-6) have been found in tumors in a number of studies, but their direct role in cancer remains unproven.
Phases of herpesvirus infection
Herpesvirus infection goes through three main phases. First – **primary infection**: the virus enters through mucous membranes or skin, uses special proteins to attach and penetrate the cell. Then the virus spreads to its “reservoir” cells: HSV-1 and VZV populate nerve ganglia, EBV – B cells, CMV – monocytes and other immune cells. In the **latent phase**, the virus practically “sleeps”: its DNA exists in the cell in the form of a closed ring, and almost no new viral proteins are synthesized. In this way, the immune system does not have time to distinguish the infected cell. Finally, under the influence of triggers (stress, weakened immunity, illness or injury), the virus **reactivates**. At this point, it begins to copy its DNA multiple times and collect new virus particles that can cause repeated rashes or other symptoms.
Main complications by organ systems
- Nervous system: herpesviruses can cause meningitis or encephalitis (inflammation of the brain) – these are the most dangerous complications. HSV-1 and HSV-2 can cause severe damage to the brain and nerves, and Varicella-Zoster (chicken pox virus) can cause neuritis (painful rashes on the side of the nerve).
- Skin and mucous membranes: recurrent blistering rashes on the lips (herpes simplex), around the genitals (genital herpes), on the skin (herpetic rash). In immune-dependent cases, rashes can spread or be complicated by infections.
- Eye: herpesvirus eye lesions – keratitis (inflammation of the cornea) in HSV-1, retinitis (inflammation of the retina) in CMV, which can lead to vision loss.
- Gastrointestinal tract: in people with weakened immunity (for example, after transplantation), CMV can cause inflammation of the stomach and intestines; EBV can cause inflammation of the liver. In general, generalized herpesvirus infections can affect many organs.
- Congenital complications: CMV is the most common virus that causes birth defects (infection during pregnancy can cause deafness or developmental disabilities). HSV, if it infects a baby at birth, can cause severe brain damage (neonatal herpes).
- Musculoskeletal system: although rare, some herpesviruses can cause myositis (inflammation of the muscles) or rheumatoid-like symptoms in immunocompromised people.
Diagnosis and therapy
To establish a herpes infection, doctors use modern methods: the most accurate is DNA analysis of the virus (PCR) in material from lesions or blood. They also do a blood test for specific antibodies (IgM/IgG) to the virus. This allows you to determine whether the infection is fresh or has been carried for a long time in a latent form.
Antiviral drugs are mainly used for treatment: acyclovir, valacyclovir, ganciclovir, valganciclovir, foscarnet, cidofovir. They reduce symptoms and shorten the duration of rashes, but do not completely eradicate the virus. Immunoglobulins (specific for the virus) can be added to severe infections or immunodeficient patients. Regarding prevention: currently there is a vaccine only against the varicella-zoster virus; vaccines against HSV-1/2 or other herpes are not yet available. Scientists are working on new vaccine and immune therapies – for example, investigating mRNA-based vaccine models for HSV and the use of T lymphocytes to prevent EBV-associated lymphomas.
All herpesviruses go through three key phases:
1. Primary infection
The virus enters the body through mucous membranes or skin.
2. Latency (hidden phase)
The virus “falls asleep” in the cells and almost does not manifest itself.
3. Reactivation
In case of stress, immune deficiency or illness, the virus is reactivated.
It is this third phase that is often associated with chronic symptoms that are difficult to explain.
The main types of herpesviruses and their role
HSV-1 (herpes simplex virus type 1)
Most often it manifests itself as “herpes on the lips”. But also capable of:
- affect the nervous system (encephalitis)
- affect cognitive processes
- be associated with neurodegenerative changes
HSV-2
Mostly causes genital herpes, but also:
- can cause chronic pain
- affects the nervous system
VZV (HHV-3, varicella zoster virus)
After chickenpox is transferred, it remains in the nerve ganglia and can cause:
- shingles
- postherpetic neuralgia
EBV (HHV-4)
One of the most systemically significant viruses:
- infects B-lymphocytes
- associated with multiple sclerosis
- associated with lymphomas
- can cause chronic fatigue
CMV (HHV-5)
It is especially dangerous with immunodeficiency:
- eye damage (retinitis)
- lesions of the gastrointestinal tract
- congenital infections
HHV-6
One of the key but underrated viruses:
- infects T-lymphocytes
- can integrate into the human genome (ciHHV-6)
- associated with:
- chronic fatigue
- neurological symptoms
- demyelination
It is HHV-6 that is often suspected in the “gray zone” of symptoms without a clear diagnosis.
HHV-7
Less studied, but very important:
- often co-activated with HHV-6
- affects immune regulation
- can support chronic inflammatory processes
Its role is often underestimated because standard diagnostics rarely take it into account.
HHV-8 (KSHV)
Known as Kaposi’s sarcoma virus:
- causes oncological processes
- especially active in immunodeficiency
Complications that can cause herpesviruses
Herpesviruses can affect different systems:
- Nervous system: encephalitis, cognitive impairment
- Immune system: imbalance, autoimmune processes
- Skin: recurrent rashes
- Eyes: keratitis, retinitis
- Oncology: lymphomas, Kaposi’s sarcoma
Diagnostics
Main methods:
- PCR — determines the DNA of the virus
- IgM/IgG antibodies — show the infection phase
It is important to understand that standard tests do not always reflect latent activity.
Treatment and control
Main drugs:
- acyclovir
- valacyclovir
- ganciclovir
- valganciclovir
They do not destroy the virus completely, but:
- reduce symptoms
- control reactivation
New approaches are also being explored:
- mRNA vaccines
- T-cell therapy
- targeted immunotherapy
What is important to understand
Herpes viruses are not always a “here and now” problem. Often it is a long-term process, which can manifest itself for years.
That is why in difficult cases it is important to look at the situation systematically.
Research perspectives and knowledge gaps
- More research is needed on the relationship between herpesviruses and chronic diseases. Many observations (for example, about herpes and dementia) need to be confirmed by large clinical studies.
- The main medical task is to create a vaccine against HSV and CMV, which could really prevent diseases or completely eliminate the virus from the body.
- It is necessary to better learn how to completely destroy the latent virus (not just temporarily silence it). For example, innovative methods based on genetic technologies or “immune hacks” for finding and destroying infected cells are possible.
- Multidisciplinary research is recommended, combining cell experiments, patient blood tests, and clinical trials to understand how herpes is linked to the immune system and disease risk.
Conclusions for clinicians and researchers
It is important for doctors to remember that herpes viruses can cause not only obvious ulcers, but also other symptoms. For example, patients with neurological or immunogenic problems should think about the herpetic nature of the disease. Timely administration of antiviral drugs can prevent complications and possibly reduce the risk of developing dementia in elderly patients. For scientists, the conclusion is obvious: it is necessary to continue the search for new drugs and vaccines. Especially promising are studies that combine the effect of the virus on the cell with real data on patients. This will make it possible to create more accurate methods of prevention and therapy of herpes virus infections.
- Chang S-T. et al. Anti-herpetic treatment reduces dementia risk: A systematic review and meta-analysis. Journal of Alzheimer’s Disease, 2026.
- Liu Y. et al. Association between herpes simplex virus type 1 and the risk of Alzheimer’s disease: a retrospective case–control study. BMJ Open, 2025.
- Devanand D.P. et al. Valacyclovir Treatment of Alzheimer’s Disease (VALAD) Trial: protocol for a randomized controlled trial. BMJ Open, 2020.
- Drinkall N.J. et al. Herpesviruses, antiviral treatment, and the risk of dementia – systematic review and meta-analysis. Alzheimer’s Research & Therapy, 2025.
<
Warning: This material contains medical information. It is not a substitute for a doctor’s consultation. In case of health problems, consult a specialist.
Sources
- Herpes simplex virus – Fact Sheet (WHO, May 30, 2025)
- Cohen J.I. Herpesvirus latency. J. Clin. Invest. (2020)
- Genital Herpes – CDC (February 20, 2024)
- Shu C. et al. Mechanistic insights into HSV-1 in Alzheimer’s disease. Front. Aging Neurosci. (2023)
- Chang S-T. et al. Anti-herpetic treatment reduces dementia risk. J. Alzheimer’s Dis. (2025)
- Otero C.E. et al. Human herpesvirus evasion and vaccine development. Nat. Rev. Microbiol. (2026)
АС