Herpesvirus infections

Herpes virus infections are a group of widespread anthroponous infectious diseases caused by viruses of the Herpesviridae family that are characterized by a chronic recurrent course and lifelong persistence of the pathogen in the body.

ICD-10 codes

• B00. Infection caused by the herpes simplex virus Herpes simplex (herpetic infection).
• Q01. Chicken pox (Varicella zoster).
• B02. Shingles (Herpes zoster).
• B08.2. Exanthema sudden (sixth disease).
• Q25. Cytomegalovirus disease.
• Q27. Infectious mononucleosis.

Epidemiology of herpesvirus infections

The source of herpesviruses - patients with acute forms of diseases (stomatitis, genital herpes, chicken pox, etc.) and healthy persons infected with the corresponding virus, which periodically release it into the environment with saliva, nasopharyngeal secretion, secretion of the mucous membranes of the genital organs. It has been established that by the age of 18 more than 90% of urban residents have been infected with one or more of seven clinically relevant herpesviruses (HSV type 1 and 2, varicella zoster virus, CMV, EBV, HHV-6 and -8). In most cases, primary and re-infection occurs by airborne droplets, with direct contact or through household items and hygiene (common towels, handkerchiefs, etc.). Oral and genital are also proved. Orogenital. Vertical, transfusion and transplantation pathways of infection.

[1], [2], [3], [4], [5], [6], [7], [8],

What causes herpesvirus infections?

Herpesviruses can circulate in the body with a normal immune system asymptomatically, but people with depressed immunity can cause serious diseases with a fatal outcome. Herpesviruses have oncogenic activity and play an important role in the development of some types of lymphomas, cervical cancer, Kaposi's sarcoma, etc.

Herpesviruses are united in a vast family of Herpesviridae, which includes more than 100 representatives, of which 8 herpesviruses are human pathogens - human herpes virus ( HHV). Herpesviruses are a phylogenetically ancient family of large DNA viruses; they are divided into three subfamilies depending on the type of cells in which the infectious process takes place, the nature of the virus reproduction, the structure of the genome, the molecular biological and immunological features: α, β and γ.

Different kinds of herpes

Name	Abbreviation	Synonym	Symptoms
HSV type 1 (Herpes simplex Type 1)	HSV-1, HHV-1 / HSV-1, HHV-1 (α-herpesvirus)	Bubble lichen virus	Oral-facial lesions, aphthous-ulcerative stomatitis, labial herpes, herpetic dermatitis, herpetiform eczema, keratitis, conjunctivitis, encephalitis
HSV type 2 (Herpes simplex Type 2)	HSV-2, HHV-2 / HSV-2, HHV-2 (α-herpesvirus)	Genital herpes virus	Genital lesions of mucous membranes, meningitis
Chickenpox virus, human herpesvirus type 3 (Varicella Zoster virus, Human herpes virus Type 3)	HSV-3, HHV-3, varicella zoster virus, HZV, HHV-3 (α-herpesvirus)	Shingles virus, Herpes Zoster	Varicella, surrounding the lesion along the sensitive nerve endings, pre- and perinatal infections
EBV, human herpesvirus type 4 (Epstein-Barr virus, Human herpes virus Type 4)	EBV. HHV-4 EBV, HHV-4 (γ-herpesvirus)	Infectious mononucleosis virus	Infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, lymphoepithelioma of the salivary gland, hepatitis
CMV, human herpesvirus type 5 (Cytomegalovirus, Human herpes virus Type 5)	CMV, HHV-5TCMV, HHV beta-herpesvirus)	Cytomegalovirus	Pre- and perinatal infection, teratogenic effect, immunodeficiency, liver, kidney, lung, eye, lymph nodes, CNS. Propensity to generalize infection
Human herpes virus Type 6 (Human herpes virus Type 6)	HHV-6, HHV-6 (β-herpesvirus)	Human In lymphotropic virus	Sudden exanthema of children, mononucleoside syndrome, chronic fatigue syndrome, encephalomyelitis, cofactor of HIV infection, oral and cervical carcinomas
Herpes simplex virus type 7 (Human herpes virus Type 7)	HHV-7, HHV-7 (β-herpesvirus)		Sudden exanthema of children, chronic fatigue syndrome
Herpesvirus associated with Kaposi's sarcoma, the human herpes virus type 8 (Kaposi's sarcoma associated herpesvirus, Human herpes virus Type 8)	FHVC, HHV-8, KSHV, HHV-8 (γ-herpesvirus)		Kaposi's Sarcoma, primary common lymphoma

α-Herpesviruses, including HHV-1, HHV-2 and varicella zoster virus (Varicella zoster virus), are characterized by rapid viral replication and cytopathic action on cultures of infected cells. Reproduction of α-herpesviruses occurs in various types of cells, viruses can persist in a latent form, mainly in the nerve ganglia.

β-Herpesviruses are species-specific, affect various types of cells, which in this case increase in size (cytomegaly). May cause immunosuppressive conditions. Infection can take a generalized or latent form; a persistent infection appears easily in the cell culture. This group includes CMV, HHV-6, HHV-7.

γ-Herpesviruses are characterized by tropism to the lymphoid cells (T and B lymphocytes), in which they persist for a long time and can transform, causing lymphomas, sarcomas. This group includes EBV and HHV-8 herpesvirus. Associated with Kaposi's sarcoma.

All herpesviruses are similar in morphological features, size, nucleic acid type (double-stranded DNA), icosaadeltahedral capsid (its assembly takes place in the nucleus of the infected cell), the coat, the type of reproduction, the ability to cause chronic and latent infection in humans.

Herpesvirus virions are extremely thermolabile - they are inactivated at a temperature of 50-52 ° C for 30 minutes, at a temperature of 37.5 ° C for 20 hours, are stable at -70 ° C; well tolerate lyophilization, persistently stored in tissues in a 50% solution of glycerin. On metal surfaces (coins, door handles, water faucets), herpesviruses survive for 2 hours, on plastic and wood - up to 3 hours in moist medical cotton wool and gauze - during their entire drying time at room temperature (up to 6 hours). The unique biological properties of all human herpesviruses are tissue tropism, the ability to persistence and latency in the body of an infected person. Persistence is the ability of herpesviruses to continuously or cyclically multiply (replicate) in infected cells of tropic tissues, which creates a constant threat of the development of the infectious process. The latency of herpesviruses is a lifelong retention of viruses in a morphologically and immunochemically modified form in the nerve cells of regional (in relation to the site of herpesvirus) ganglia of sensory nerves. Strains of herpesviruses have unequal capacity for persistence and latency and sensitivity to antiherpetic drugs due to the peculiarities of their enzyme systems. Each herpesvirus has its own rate of persistence and latency. Among the studied, the most active in this regard are HSV, the least is EBV.

The pathogenesis of herpesvirus infections

Human infection with these herpesviruses is accompanied by clinical symptoms of the corresponding acute infection, on average, no more than 50% of people, mainly children: sudden exanthema (HHV-6), aphthous stomatitis (HSV type 1 or 2), chicken pox pox Varicella zoster virus), infectious mononucleosis (EBV). Mononucleoside-like syndrome (CMV). In other patients, the infection is asymptomatic, which is especially common in adolescents and adults. In addition to the biological properties of the herpesvirus strain, the specific (age, sex, phylo- and ontogenetic) features of the immune response of the infected person to the numerous antigens of the virus exert their influence on the course of acute and recurrent herpesvirus diseases.

With a decrease in the immunoreactivity of the organism, herpesviruses act as opportunistic viruses, leading to a more severe, with unusual clinical manifestations, course of the underlying disease. Called HSV, CMV, EBV diseases are considered as AIDS-indicator in connection with their frequent detection in this pathology.

The role of some herpesviruses (HHV-8, CMV, EBV, etc.) in the development of a number of malignant neoplasms: nasopharyngeal carcinoma, Burkitt's lymphoma, B-cell lymphoma, breast cancer, adenocarcinoma of the intestine and prostate, carcinoma of the cervical canal of the cervix, Kaposi's sarcoma, neuroblastoma and others.

The greatest threat to health is represented by herpetic neuroinfections (lethality reaches 20%, and the incidence of disability is 50%), ophthalmoherpes (in almost half of patients leads to the development of cataracts or glaucoma) and genital herpes.

All known herpesvirus infections can recur, however, the threshold and causes of the transformation of the acute form into recurrent for each type of herpesvirus are different. For example, the recurrence of infections caused by HSV often occurs against stress, nonspecific endocrine disorders, changes in the geographical area of residence, hyperinsolations, etc. In elderly people who have had chicken pox in childhood, recurrence of infection caused by the varicella zoster virus (Varicella zoster virus) , proceeds in the form of herpes zoster. Subclinical relapses of CMVI are most often observed in pregnant women and patients receiving immunosuppressive therapy. At the same time, infections caused by EBV recur very rarely and only in patients with congenital or acquired immunodeficiency.

Cloning of herpesviruses occurs according to the following scheme: spontaneous accidental adsorption of the original "mother" virus on the surface of the target cell, "stripping of the virion" - cleavage of the envelope and capsid, infiltration of the viral DNA into the nucleus of the target cell, formation and maturation of "daughter" virions by budding on nuclear membrane. All these transformations are controlled by enzymatic systems of viral origin. During the maturation of "daughter" virions, their envelopes, capsids and DNA are formed from amino acids, proteins, lipoproteins and nucleosides present inside the infected cell. These molecules enter the infected cell from the interstitial spaces as the intracellular reserves deplete. The first generation of "daughter" herpesviruses begins to enter the environment (intercellular spaces, blood, lymph and other biological media) after about 18 hours. In the free state, herpesviruses are kept for a very short period (from 1 to 4 hours) - this is the typical duration period of acute intoxication with herpes virus infections. The life expectancy of each generation of formed and adsorbed herpesviruses on average is 3 days.

Symptoms of herpesvirus infections

For practical purposes, herpesviral infections are classified with simultaneous localization of the process, recurrence and etiology.

Acute and recurrent herpesvirus diseases

Herpesvirus type	Primary diseases	Recurrent diseases
HSV type 1	Gingivostomatitis. Keratoconjunctivitis	Oral herpes, keratoconjunctivitis, encephalitis
HSV type 2	Genital herpes, neonatal herpes, disseminated herpes	Genital herpes
Chicken pox virus (Varicella zoster virus)	Chickenpox	Herpes zoster, disseminated varicella in immunodeficiency
EOB	Infectious mononucleosis, B-cell proliferation	Infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma
CMV	Congenital anomalies, cytomegaly in immunodeficiency	Cytomegaly in patients after organ transplantation, retinitis, colitis or neuroinfection with AIDS
Herpes simplex virus 6	Erythema of newborns	Systemic diseases after transplantation
Human herpes virus 7	Erythema of newborns	Unknown
Human herpes virus 8	Kaposi's Sarcoma	Unknown

Diagnosis of herpesvirus infections

Diagnosis of herpesvirus infections is based on the use of ELISA, the method of immunofluorescent antibodies, IB, PCR, electron microscopy.

[9], [10], [11], [12], [13], [14], [15],

Treatment of herpesvirus infections

Treatment of herpesvirus infections remains a challenge. A prolonged chronic process leads to a negative immune restructuring of the organism: development of secondary immune deficiency, suppression of cellular immunity reactions, reduction of nonspecific defense of the organism, expressed in decreasing the ability of leukocytes to produce a- and y-interferon, hypoimmunoglobulinemia, sensibilisation to antigens of the virus. Given the etiology, pathogenesis, symptoms of herpesvirus infections, for the treatment of herpetic diseases, numerous preparations of etiotropic and immunocorrective action have been proposed, which are divided into three groups according to the mechanism of action.