Morphology and structure of the herpes virus. Herpes simplex virus

Taxonomy: Family Herpesviridae. Subfamily Alphaherpesviruses, genus Simplexvirus

Virus properties:

Structure. The HSV genome encodes about 80 proteins necessary for virus reproduction and the latter’s interaction with the body’s cells and the immune response. HSV encodes 11 glycoproteins

Cultivation. To cultivate the virus, a chicken embryo is used (small dense plaques form on the shell) and a cell culture, in which it causes a cytopathic effect in the form of the appearance of giant multinucleated cells with intranuclear inclusions.

Antigenic structure. The virus contains a number of antigens associated with both internal proteins and glycoproteins of the outer shell. The latter are the main immunogens that induce the production of antibodies and cellular immunity. There are two serotypes: HSV type 1 and HSV type 2.

Resistance. The virus is unstable and sensitive to sunlight and UV rays.

Epidemiology. The source of infection is the patient.

HSV-1 and HSV-2 are transmitted primarily by contact (with vesicular fluid, saliva, sexual contact), through household items, and less often by airborne droplets, through the placenta, and at the birth of a child.

Both types of viruses can cause oral and genital herpes. HSV-1 most often affects the mucous membranes of the oral cavity and pharynx, causing encephalitis, and HSV-2 - the genitals (genital herpes).

Pathogenesis. There are primary and recurrent herpes simplex. More often, the virus causes an asymptomatic or latent infection.

Primary infection. Vesicle is a manifestation of herpes simplex with degeneration of epithelial cells. The basis of the vesicle is made up of multinucleated cells. The affected cell nuclei contain eosinophilic inclusions. After some time, the top of the vesicle is opened, and an ulcer is formed, which is soon covered with a scab, forming a crust, followed by healing.

Bypassing the entrance gate of the epithelium, viruses pass through sensitive nerve endings with further movement of nucleocapsids along the axon to the neuron body in sensory ganglia. Reproduction of the virus in a neuron ends in its death. Some herpes viruses, reaching ganglion cells, can lead to the development of a latent infection, in which the neurons do not die, but contain the viral genome. Most people (70-90%) are lifelong carriers of the virus, which persists in the ganglia, causing a latent persistent infection in neurons.

Latent infection sensory neurons is a characteristic feature of neurotropic herpes viruses HSV. In latently infected neurons, about 1% of cells in the affected ganglion carry the viral genome.

Clinic. The incubation period is 2-12 days. The disease begins with the appearance of itching, swelling and blisters filled with liquid in the affected areas. HSV affects the skin (vesicles, eczema), mucous membranes of the mouth, pharynx (stomatitis) and intestines, liver (hepatitis), eyes (keratitis) and central nervous system (encephalitis). Recurrent herpes is caused by reactivation of the virus preserved in the ganglia. It is characterized by repeated rashes and damage to organs and tissues.

Genital infection is the result of autoinoculation from other affected areas of the body; but the most common route of infection is sexual. The lesion manifests itself in the formation of a vesicle, which ulcerates quite quickly.

The herpes simplex virus enters during the passage of a newborn through the mother's birth canal, causing neonatal herpes. Neonatal herpes is detected on the 6th day after birth. The virus disseminates into internal organs with the development of generalized sepsis.

Immunity. The main immunity is cellular. HRT develops.

Microbiological diagnostics. The contents of herpetic vesicles, saliva, scrapings from the cornea, blood, and cerebrospinal fluid are used. In stained smears, giant multinucleated cells, cells with enlarged cytoplasm and intranuclear inclusions are observed.

To isolate the virus, HeLa, Hep-2 cells, and human embryonic fibroblasts are infected with the test material.

Causative agents of gas anaerobic infection. Morphology, biology. Toxins and toxin-enzymes. Laboratory diagnosis, accelerated diagnostic methods. Epidemiology. Serotherapy and seroprophylaxis. Active immunization.

Anaerobic infection is a disease caused by obligate anaerobic bacteria under conditions favorable to the life of these microbes. Anaerobes can affect any organs and tissues. Obligate anaerobes are divided into two groups: 1) bacteria that form spores (clostridia) and 2) non-spore-forming or so-called non-clostridial anaerobes. The former cause clostridiosis, the latter cause purulent-inflammatory diseases of various localizations. Representatives of both groups of bacteria belong to opportunistic microbes.

Gas gangrene- wound infection caused by bacteria of the genus Clostridium is characterized by rapidly occurring necrosis of predominantly muscle tissue, severe intoxication and the absence of pronounced inflammatory phenomena.

Taxonomy. The causative agents are several species of the genus Clostridium, division Firmicutes. The main representatives are C.perfringens, C.novii, C.ramosum, C.septicum, etc. C.perfringens takes first place in terms of frequency of occurrence and severity of the disease caused.

Morphological and cultural properties. Rod-shaped, gram-positive bacteria that form spores. In the affected tissues, gas gangrene clostridia form capsules that have antiphagocytic activity, and when released into the environment, they form spores.

Antigenic properties and toxin formation: Each type of clostridia is divided into serovars that produce exotoxins and differ in antigenic properties. For example, C. perfringens toxin is divided into 6 serovars: A, B, C, D, E and F. Of these, A and F are pathogenic for humans, the rest are pathogenic for animals. C. novii, based on the antigenic properties of the toxin, is divided into serovars A, B, C and D. Some toxins have enzyme properties.

Pathogenicity factors: Clostridia of gas gangrene produce an exotoxin - a-toxin, which is a lecithinase, as well as hemolysins, collagenase, hyaluronidase and DNase. Exotoxins are specific to each type of clostridia.

Epidemiology. In case of severe injuries and untimely surgical treatment of wounds. In the epidemiology of gas gangrene, soil contamination of wounds is of great importance.

Pathogenesis. A number of conditions contribute to the occurrence of gas gangrene: the entry of microbes into the wound (the disease is usually caused by the association of several types of anaerobes and, less often, one of them), the presence of necrotic tissue, and decreased resistance. In necrotic tissues, anaerobes often find hypoxic conditions favorable for their reproduction. The toxins and enzymes they produce lead to damage to healthy tissues and severe general intoxication of the body; α-toxin, lecithinase, breaks down lecithin, an important component of cell membranes. The secreted hyaluronidase and collagenase increase tissue permeability and also contribute to the spread of the microbe in the surrounding tissue.

Clinic: The incubation period is short - 1-3 days. Swelling, gas formation in the wound, with severe intoxication of the body.

Immunity: The infection does not leave immunity. Antitoxins play a leading role in protecting against toxins.

Microbiological diagnostics: The material for research (pieces of affected tissue, wound discharge) is microscopically examined. The diagnosis is confirmed by detecting gram “+” rods in the material in the absence of leukocytes. A bacteriological study is carried out - detection of C. perfringens in feces - foodborne toxic infection;

Treatment: Surgical: necrotic tissue is removed. Antitoxic serums are administered, antibiotics and hyperbaric oxygen therapy are used.

Antitoxic serums - in liquid and dry form after purification by enzymatic hydrolysis of anatoxic sera obtained from immunization of horses with toxoids. Used for emergency prevention and specific therapy.

Prevention: Surgical treatment of wounds, compliance with asepsis and antisepsis during operations. For specific active immunization, an toxoid is used in the composition of sextanatoxin, which creates acquired, artificial, active, antitoxic immunity.

• Annotation:
  The herpes virus and the diseases it causes: herpes simplex, chickenpox, shingles, etc. are widely distributed on Earth. The name herpes was coined by doctors in Ancient Greece and comes from the Latin verb herpain, which means “to crawl.” This name is explained by the fact that it spreads spreading in the form of characteristic vesicular rashes on the patient’s skin. Herpes was first described in scientific literature by doctors of Ancient Rome approximately a thousand years BC. Herpes became a problem that attracted public attention in the 20th century. This insidious virus is among the most common human diseases transmitted as a viral infection. Herpes is an important and difficult problem to solve in modern society and medicine. Nine out of ten people in the world suffer from herpes simplex, and every fifth person has manifestations of herpes in the form of a cold rash. There are quite a few clinical manifestations of herpes, and they are all of different types: not only the skin can be affected, but also the eyes, oral cavity, nervous system of a patient with herpes, his respiratory system and genitals. Due to its neurodermatropism, herpes causes skin rashes and damage to the mucous membranes of the body. The destructive effects that herpes has on the patient’s central nervous system cause diseases such as encephalitis and meningitis. With herpes, eye diseases are also possible; keratitis or conjunctivitis. Herpes simplex can cause pathologies in pregnant women during fetal maturation and childbirth; in some cases, spontaneous, unintentional abortion or death of the fetus occurs in the womb of a mother with herpes. Also, a newborn child may have herpes in a generalized form. Researchers have noted a connection between genital herpes in men (prostate cancer) and women (cervical cancer). Statistics from recent years show that the incidence of herpes is constantly increasing - this cannot but be alarming. In the United States, according to research, about 40 million people suffer from genital herpes, and in one year this number increases by an average of half a million people. One in five Americans, when examined, show clinical signs that they have once had an infection caused by the herpes virus. In Russia, the situation also looks far from the best - every year about two million people with herpes are admitted to Russian hospitals. To know this dangerous virus, you need to research it. This scientific review by Ph.D. O.V. Mosina introduces the reader to genetic and biochemical studies of herpes viruses and the mechanism of their replication in cells.

In recent years, herpes viruses (from the Greek herpes - creeping) have become increasingly important in infectious pathology. The attention that virologists and clinicians have shown over the past 25 years to human herpes viral diseases is associated with their significant epidemiological role and social significance in the modern world. The steady increase in the number of herpetic diseases in adults and children necessitates a comprehensive study of herpetic infection and the development of effective methods for the prevention and treatment of various forms of this infection. Among viral infections, herpes occupies one of the leading places due to the ubiquity of viruses, the variety of clinical manifestations, usually chronic, as well as the various routes of transmission of viruses.

It is among the most common and poorly controlled human infections. Herpes viruses can circulate asymptomatically in bodies with a normal immune system, but cause severe illness and death in people with immunosuppression. According to WHO, mortality from herpes infection among viral diseases is in second place (15.8%) after hepatitis (35.8%).

Herpes viruses are united into a large family Herpesviridae and are currently most clearly classified. Family Herpesviridae includes more than 80 representatives, 8 of which are the most pathogenic for humans (human herpes virus-HHV). Herpes viruses - a phylogenetically ancient family of large DNA viruses - are divided into 3 subfamilies depending on the type of cells in which the infectious process occurs, the nature of virus reproduction, genome structure, molecular biological and immunological features: α, β and γ ( , according to N. G. Perminov, I. V. Timofeev and others, State Scientific Center for Virology and Biotechnology).

α-herpes viruses, including HSV-1, HSV-2 and VZV, are characterized by rapid viral replication and a cytopathic effect on infected cell cultures. Reproduction of α-herpes viruses occurs in various types of cells; viruses can remain in latent form, mainly in ganglia.

β-herpes viruses are species-specific, affect various types of cells, which at the same time increase in size (cytomegaly), and can cause immunosuppressive conditions. The infection can take a generalized or latent form; persistent infection easily occurs in cell culture. This group includes CMV, HHV-6, HHV-7.

γ-herpes viruses are characterized by tropism for lymphoid cells (T- and B-lymphocytes), in which they persist for a long time and which can transform, causing lymphomas and sarcomas. This group includes Epstein-Barr virus and HHV-8 herpes-Kaposi's sarcoma-associated virus (KSHV). KSHV is most closely related in genomic organization to the T-cell-tropic simian herpesvirus Saimiri (HVS).

Herpes viruses are associated with malignancy and are capable (at least EBV and HVS) of transforming cells in vitro. All herpes viruses are similar in morphological characteristics, size, type of nucleic acid (double-stranded DNA), icosadeltahedral capsid, the assembly of which occurs in the nucleus of the infected cell, envelope, type of reproduction, and the ability to cause chronic and latent infection in humans.

Cloning of herpes viruses occurs according to the following scheme: spontaneous random adsorption of the original “mother” virus on the surface of the target cell, “undressing of the virion” - splitting of the envelope and capsid, infiltration of viral DNA into the nucleus of the target cell, formation and maturation of “daughter” virions by budding on the nuclear membrane. After infection of a cell, for example, with herpes simplex virus types 1 or 2, the synthesis of new viral proteins begins after 2 hours, and their number reaches a maximum after about 8 hours. During the maturation of “daughter” virions, their shells, capsids and DNA are formed from those present inside the infected cell amino acids, proteins, lipoproteins and nucleosides. These molecules enter the infected cell from the interstitial spaces as intracellular reserves are depleted. In this regard, viruses depend on the intensity of intracellular metabolism, which, in turn, is determined by the nature of the target cell. The highest rate of metabolism is characteristic of short-lived cells of the epithelioid type, therefore herpes viruses colonize epithelial and mucous membrane cells, blood and lymphatic tissues especially well. Fully formed and ready for subsequent active reproduction, “daughter” infectious virions appear inside the infected cell after 10 hours, and their number becomes maximum after about 15 hours. The number of virions to a certain extent affects the rate of spread of infection and the affected area.

The first generation of “daughter” herpes viruses begins to enter the environment (intercellular spaces, blood, lymph and other biological media) after about 18 hours. This can be observed in clinical practice with uncontrolled processes (for example, with chickenpox, herpes zoster, generalization cytomegalovirus infection) - elements of a herpetic rash appear on the skin or mucous membranes in waves. In a free state, herpes viruses remain for a very short period (from 1 to 4 hours) - this is the duration that is typical for the period of acute intoxication during herpes viral infections. The lifespan of each generation of formed and adsorbed herpes viruses is on average 3 days.

From an epidemiological perspective, the following information about herpes viruses is most interesting: virions are extremely thermolabile - inactivated at a temperature of 50-52°C for 30 minutes, at a temperature of 37.5°C for 20 hours, stable at a temperature of 70°C; They tolerate lyophilization well and are stored in tissues for a long time in a 50% glycerol solution. On metal surfaces (coins, door handles, water taps) herpes viruses survive for 2 hours, on plastic and wood - up to 3 hours, in damp medical cotton wool and gauze - until they dry at room temperature (up to 6 hours).

The unique biological properties of all human herpes viruses are tissue tropism, the ability for persistence and latency in the body of an infected person. Persistence is the ability of herpes viruses to continuously or cyclically multiply (replicate) in infected cells of tropic tissues, which creates a constant threat of development of the infectious process. Latency of herpes viruses is the lifelong preservation of viruses in a morphologically and immunochemically modified form in the nerve cells of the regional (relative to the site of introduction of the herpes virus) ganglia of sensory nerves. Strains of herpes viruses have different abilities for persistence and latency and sensitivity to antiherpetic drugs due to the characteristics of their enzyme systems. Each herpes virus has its own rate of persistence and latency. Among those studied, the most active in this regard are herpes simplex viruses, the least active is the Epstein-Barr virus.

According to numerous studies, by the age of 18, more than 90% of city residents are infected with one or more strains of at least 7 clinically significant herpes viruses (herpes simplex types 1 and 2, varicella zoster, cytomegalovirus, Epstein-Barr, human herpes types 6 and 8 ). In most cases, primary and re-infection occurs by airborne droplets, through direct contact or through household and hygiene items (shared towels, handkerchiefs, etc.). Oral, genital, orogenital, transfusion, transplantation and transplacental routes of transmission of infection have also been proven.

Herpes viral infections are widespread in the world and tend to grow steadily. A feature of herpes viral infection is the possibility of involving many organs and systems in the infectious process, which determines the variety of diseases caused by herpes viruses, ranging from simple mucocutaneous infections to life-threatening generalized infections. An important property of herpes viruses is the ability, after primary infection in childhood, to persist in the body for life and be reactivated under the influence of various exo- and endogenous provoking factors.

Infection of a person with these herpes viruses is accompanied by clinical symptoms of the corresponding acute infectious disease on average in no more than 50% of people, mainly in children: sudden erythema (human herpes virus type 6), aphthous stomatitis (herpes simplex viruses types 1 or 2), chickenpox (varicella-zoster virus), infectious mononucleosis (Epstein-Barr virus), mononucleosis-like syndrome (cytomegalovirus). In other patients, the infection is asymptomatic, which is especially typical for adolescents and adults. In addition to the biological properties of the herpes virus strain, the course of acute and recurrent herpes viral diseases is influenced by the individual (age, gender, phylo- and oncogenetic) characteristics of the immune response of an infected person to numerous virus antigens.

Often, especially when the body’s immunoreactivity decreases, herpes viruses act as opportunist viruses, leading to a more severe course of the underlying disease with unusual clinical manifestations. Herpes simplex viruses types 1 and 2, as well as CMV, are among the causative agents of TORCH infections. They play an important role in disrupting human reproductive function and in the development of serious diseases of the mother, fetus, newborn and young children.

Diseases caused by the HSV, CMV, and EBV viruses are considered as AIDS indicators due to their frequent detection in this pathology. In 1988, they were included in the expanded definition of cases subject to epidemiological surveillance for AIDS. The results of recent studies indicate the role of some herpes viruses (HHV-8, CMV, EBV, etc.) in the development of a number of malignant neoplasms: nasopharyngeal carcinoma, Burkitt's lymphoma, B-cell lymphoma, breast cancer, intestinal and prostate adenocarcinoma, cervical carcinoma cervical canal, Kaposi's sarcoma, neuroblastoma, etc.

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

Apparently, all known herpes virus infections can recur, but the threshold and reasons for the transformation of an acute form into a recurrent one are different for each type of herpes virus. In general, herpes viral infections take a recurrent course in no more than 8-20% of patients. Recurrent herpes viral diseases in some people can be perceived as “chronic” when they develop over many years, not only destroying physical health and the functions of vital systems, but also psychologically having an extremely adverse effect on the patient. Therefore, for practical purposes, herpes viral infections are classified taking into account simultaneously the localization of the process, recurrence and etiology ( ).

The causes of the recurrent course of herpes viral infections are diverse. One of them is that the transformation of an acute herpes viral process into a chronic one occurs with the obvious “connivance” of the immune system. If acquired immunodeficiency as a result of chemotherapy or HIV infection is easily explained, then all attempts to find out what causes the main defect in the immune response in immunologically complete people with recurrent herpes viral infection have been unsuccessful. Another reason is, apparently, the quantitative and qualitative features of the persistence and latency of a particular strain of herpes virus in the patient’s body.

Diagnosis of herpetic infection

All methods for indicating and identifying viruses are based on the following principles:

• detection of the virus per se (electron microscopy);
• detection and identification of viruses through cells interacting with them (accumulation of viruses in cells sensitive to them);
• detection and identification of viruses using antibodies (MFA, ELISA, RAL, IB, RN, RSK);
• detection and identification of nucleic acids (PCR, MG).

Electron microscopy: rapid diagnosis allows you to detect hepatitis B or their components directly in samples taken from the patient and give a quick answer within a few hours. The pathogen is detected using electron microscopy of clinical material with negative contrast.

Serological methods are inferior in terms of information content and sensitivity to other methods of laboratory diagnosis and do not allow us to establish the etiology of a particular form of the disease with a sufficient degree of certainty. Antibody titers increase

in the late stages (several weeks) after infection or reactivation of the virus, and at the same time it may not be observed in immunodeficient individuals. To establish a 4-fold increase in antibody titer to herpes viral infection (an indicator of primary infection), a study of paired sera is necessary. Serological tests (RSC, RN) have high specificity, but relatively low sensitivity, and in addition, are difficult to perform.

The immunofluorescent method, ELISA, RAL, and IB have received widespread practical use.

The most accurate method for diagnosing herpes viral infection is isolating the virus from various cell cultures.

To detect the herpes virus, molecular biological methods are used: polymerase chain reaction and molecular hybridization reaction, which make it possible to detect the presence of viral nucleic acid in the material under study. PCR can be considered the most sensitive and fastest reaction. The sensitivity of the method makes it possible to determine one molecule of the desired DNA in samples containing 10 cells.

Treatment of herpes infection

Treatment of herpes infection remains a challenge to this day. The chronic course of the process leads to immune restructuring of the body: the development of secondary immune deficiency, inhibition of the cellular immune response, and a decrease in the body's nonspecific defense. Despite the variety of drugs used to treat herpes infection, there are no drugs that provide a complete cure for herpes. Herpes viral infection is a difficult-to-control disease. This is due, first of all, to the variety of clinical lesions, the development of virus resistance to drugs, and the presence of molecular mimicry in herpes viruses. Therefore, to successfully treat a herpetic infection, it is necessary to choose the right antiviral drug, its dose and duration of treatment, and use a combination of various drugs. In order to increase the effectiveness of treatment, treatment regimens must also include immunobiological drugs that help correct the immune status, as well as pathogenetic agents that alleviate the patient’s condition.

Currently, all antiherpetic drugs are divided into 3 main groups of antiviral drugs ( ).

The mechanism of action of chemotherapy drugs (abnormal nucleosides: Valtrex, Vectavir, Famvir, Cymevene) is associated with inhibition of viral DNA synthesis and viral replication through competitive inhibition of viral DNA polymerase.

In immunomodulatory drugs (alpizarin, imunofan, lycopid, polyoxidonium), the active substances have immunostimulating properties in relation to cellular and humoral immunity, redox processes, and cytokine synthesis.

IFN inducer drugs (amixin, neovir, cycloferon) combine etiotropic and immunomodulatory effects. The drugs induce the formation of endogenous IFN (α, β, γ) by T- and B-lymphocytes, enterocytes, and hepatocytes.

A special place among the means of antiherpes viral therapy is occupied by the herpetic vaccine to activate cellular immunity and its immunocorrection in the remission phase. Vaccination has 2 goals: preventing primary infection and the occurrence of a state of latency, as well as preventing or alleviating the course of the disease.

However, despite the availability of an extensive list of antiherpetic drugs, herpes remains a poorly controlled infection. This is due to the genotypic characteristics of the pathogen, the long-term persistence of the virus in the body, and the formation of strains resistant to antiviral drugs. The maximum clinical effect can be obtained only with rational complex therapy of drugs with different mechanisms of action.

The St. Petersburg group of scientific virologists and infectious disease specialists, led by V. A. Isakov, proposed a program for the treatment and prevention of herpes infection (Table 4).

Advantages of complex therapy for GI.

• The combined use of antiherpetic chemotherapy drugs and immunobiological agents provides a synergistic effect.
• By reducing the dose of antiviral CPP, the likelihood of developing side effects is reduced, and the toxic effect on the patient’s body is reduced.
• The likelihood of the emergence of resistant strains of herpes viruses to this drug is reduced.
• An immunocorrective effect is achieved.
• The duration of the acute period of the disease and the duration of treatment are reduced.

Thus, GI therapy is a complex and multicomponent task.

For questions regarding literature, please contact the editor.

T. K. Kuskova, Candidate of Medical Sciences
E. G. Belova, Candidate of Medical Sciences
MGMSU, Moscow

UDC 578.3:616.523

M.T.Lutsenko, I.N.Gorikov

SOME INFORMATION ABOUT THE MORPHOLOGY OF HERPES VIRUSES AND THEIR PROPERTIES

Far Eastern Scientific Center for Physiology and Pathology of Respiration, Siberian Branch of the Russian Academy of Medical Sciences,

Blagoveshchensk

This work presents literature information characterizing the structure of herpes simplex viruses and their mechanism of interaction with target cells.

Key words: virus, herpes.

SUMMARY M.T.Lutsenko, I.N.Gorikov

SOME DATA ABOUT HERPES-VIRUSES

MORPHOLOGY AND THEIR PROPERTIES

The reference data characterizing the structure of simple herpes viruses and the mechanism of their interaction with target cells are given in the work.

Key words: virus, herpes.

In the herpes virion, 3 components are identified: 1) nucleond, localized in the central part; 2) capsid covering the nucleoid and represented by capsomeres; 3) shells that surround these structural formations. The shell of herpes virions usually retains a hexagonal shape. The shell diameter ranges from 170 to 210 nm. There are two or more nucleocapsids that have a common shell. Viral particles that do not have an envelope are often found. The capsid is usually hexagonal in shape. Each face of the capsid is an equilateral triangle consisting of 15 subunits (the interval between subunits is 3 nm). Using the negative contrast method, it was found that the capsid of herpes viruses is an icosahedron. Capsomeres are hollow structures that have a penta- and hexagonal structure in cross section. The edge of the icosahedron is represented by 5 capsomeres. The 12 vertices are formed by one of the capsomeres and are surrounded by five neighboring ones. Other capsomeres of triangle faces are also limited to five adjacent ones. The capsomere retains the shape of an elongated prism. Its dimensions are 9.5 x 12.5 nm. On a cross section of the icosahedron vertex they have a pentagonal shape. The remaining capsomeres of the capsid surface are hexagonal in shape with an internal opening up to 4 nm. Thus, the capsid of the herpes virion is represented by 162 capsomeres, which are packed in a symmetrical order, in a ratio of 5:3:2 (Fig. 1). When performing electron microscopy, virions predominate (with or without an envelope), the central part of which is not penetrated by phosphotungstic acid. These virions

are conventionally called “complete”, that is, they contain a nucleoid. At the same time, virions are identified in which phosphotungstic acid is detected in their central part. This morphological fact allows us to call them “empty” virions and assume that they lack a nucleoid. Such virions usually have a clearly contoured capsid. It contains up to 24 capsomeres. According to the author, the hexagonal space limited by the capsid shell, in which phosphotungstic acid is clearly contoured, has an average size of 78 nm (Fig. 2).

Rice. 2. Herpes simplex virus. Section of an infected fibroblast cell. Immature virions in the cell nucleus (according to A.F. Bocharov). Magnification ><160000.

Virions of herpes viruses are characterized by an irregular spherical shape. They have a diameter of 120-200 nm and 4 main components: an electron-dense core; icosahedral nucleocapsid; an electron-dense inner shell (tegument) and an outer membrane (envelope). The core consists of DNA associated with proteins. The diameter of the capsid ranges from 100 to 110 nm. It has the shape of an icosahedron, in which up to 162 capsomers (150 hexamers and 12 pentamers) are identified. The latter are placed 5 on each facet (edge). The inner shell is represented by globular protein molecules, and the outer shell is a bilayer lipid membrane with protein protrusions defined in its structure.

The genetic apparatus of herpes simplex viruses consists of linear double-stranded DNA. DNA has a molecular weight that varies from 80 to 150 x 1 dalton. The virus genome is capable of encoding over 60 gene products. More than 30 polypeptides are detected in virions: 7 glycoproteins (glycoproteins gB, gC, gD, gE gF, gG and gX) are clearly visualized on the surface and participate in the formation of virus-neutralizing antibodies. Six proteins are detected in the capsid, including ATPase and protein kinase. Other proteins (in particular, thymidine kinase) are non-structural proteins and are synthesized during virus reproduction in the host cell. In infectious agents, antigens are identified that are associated with internal protein molecules and external glycoproteins. However, the key immunogens remain gB, gC and gD. More than 20% of lipids are determined in purified complete virions.

Replication of herpes simplex viruses in a cell is a multi-step process (Fig. 3). The herpes simplex virus does not have the ability to reproduce on its own and reproduces only in a living cell. The pathogen propagation process includes the following stages:

1) interaction with the receptor on the surface of the host cell;

2) penetration into the cell;

3) shedding of the capsid;

4) transcription;

5) post-transcriptional formation of mRNA;

6) translation of viral protein;

7) protein formation and modification;

8) replication of the viral genome (DNA or RNA);

9) intracellular accumulation of viral particles;

10) removal of virions from an infected cell.

At the first stage, the herpes simplex virus interacts with the cellular receptor and enters the cell through endocytosis. When the capsid is exposed, it appears in the cytosol. The formed DNA-protein complex usually enters the nucleus. Then the capsid is destroyed and the virion DNA reaches the nucleoplasm. Here it begins to function, transcribed by cellular RNA polymerase. At

This includes ultra-early, early and late transcription, mRNA processing, as well as the synthesis of encoded products with their partial reverse transport through the karyolemma.

Rice. 3. Herpes virus replication cycle (diagram)

The DNA is then replicated to form daughter molecules as well as immature capsids. At the same time, their budding through the karyolemma is recorded, as well as the formation of mature capsids on the membrane structures of the endoplasmic reticulum, their transport to the surface through modified elements of the cytoplasmic reticulum and exit to the outside (Fig. 3). It should be noted that in the nucleus of the host cell, during the replication process, the transcription of viral DNA is recorded and the process of transformation of the formed RNA into mature mRNA occurs. In the cytoplasm of the host cell, viral mRNA is translated into protein (the largest amount is formed through cleavage and glycosylation). Herpes simplex virus gene expression is regulated by viral proteins that lead to sequential expression of mRNA and proteins. Viral DNA replication occurs in the nucleus. Viral particles are formed from newly synthesized viral DNA and viral capsid proteins inside the nuclear membrane. Virions leave infected cells through their fusion with the cell membrane or as a result of lysis of the cytolemma of cellular elements.

During the process of reproduction in an infected cell, the herpes simplex virus specifically affects its enzyme systems, especially those that are directly involved in the synthesis of the polynucleotide chain of the pathogen from nucleosides and mononucleotides (kinases, ribonucleotide reductases, DNA polymerases and nucleases). According to the authors, thymidine kinase, which catalyzes the phosphorylation of thymidine with the help of ATP and the formation of thymidine monophosphate and adenosine diphosphate, is of paramount importance in the interaction between the virus and the cell. It is known that thymidine kinase is involved in the phosphorylation of deoxycytidine, deoxycytidine, acycloguanosine, as well as some synthetic nucleosides used in the chemotherapy of this infection.

The replication of viral DNA involves the viral DNA polymerase, which interacts with the virus-induced DNA-bound protein. Last formie

forms complexes with DNA and is detected using electron microscopy.

With a primary lesion, replication of the pathogen is observed at the site of its invasion. Typically, the virus enters the ganglia through hematogenous spread or through the axoplasm. The herpes simplex virus is characterized by long-term persistence.

Latency is one of the mechanisms for preserving pathogens in the cell of the human body, the immune system of which excludes the creation of conditions for the full development of an acute infectious-inflammatory process during the interaction of a macro- and microorganism (virus). In the formation of a chronic viral infection, the following are of paramount importance:

a) the existence of genetically determined cell resistance to the herpes virus. In this case, the reproduction of pathogens occurs without a cytodestructive effect, or the selection of stable cellular elements in which virions are determined is recorded;

b) chronicity of herpes infection is observed in the case of constant exposure of the pathogen to a significant amount of inhibitors (antibodies, interferon, antiviral drugs, etc.);

c) it is possible that the evolution of various types of pathogens led to the existence of viruses in the form of nucleotides of varying degrees of heterogeneity and infectiousness of DNA-RNA transcripts in the genome of cells. These viral formations, in all likelihood, can form associations with other pathogens in cells with certain genetically determined resistance;

d) herpes viruses are identified that are resistant to immunocompetent cells;

e) often, during the interaction of herpes viruses with cells, their destruction is not observed, and in the process of division of such viruses, the transfer of the latter to daughter cells is visualized. At the same time, intracellular cytoplasmic structures take an active part in the reproduction of virions.

Triggering points in the reactivation of herpes are: fever, various stressful situations, injuries and digestive disorders. In the reactivation of persistent slow viral infections, a person’s residence in the conditions of the Asian part of the Far North of the Russian Federation plays a cardinal role. Moreover, an increase in the adsorption of the herpes virus on the cell surface at low temperatures has been experimentally established, while the remaining stages of the interaction of this pathogen with the cell membrane are mainly carried out at a higher ambient temperature. Against this background, it is impossible to exclude the specific nature of the relationship that develops between the bacterial flora that colonizes the airways, urinary, genital organs and digestive tract with viruses that are in persistent form. However, it is known

that, under certain conditions, low temperatures contribute to the preservation of the population of microorganisms and an increase in the number of their colonies. According to the authors, as the ambient temperature decreases, the virulence of bacteria increases (their mobility increases, which determines their chemotactic properties, capsule formation and synthesis of biopolymers with a toxic function, as well as enzymes characterizing the pathogenic properties of pathogens, increase). Thus, in regions with low temperatures, a special nature of the relationship between the “bacteria - DNA - viruses” system may develop. The literature provides very convincing clinical, immunological and virological data indicating the specificity of resistance of the population living in the Far North: the predominance of erased and chronic forms of diseases; low level of immunological resistance of children of the newcomer population compared to the indigenous inhabitants of the North; violation of the vaccination schedule as a result of long-term contraindications, which leads to an increase in the number of people susceptible to viral infections. It has been shown that in harsh climatic conditions the body’s resistance is affected by:

1) disadaptation of the migrating population when moving to a permanent place of residence and during short-term stays of people during vacation in the southern regions of Russia;

2) exposure to unfavorable biological, geochemical and man-made factors (polar night, deficiency of micro- and macroelements, vitamin deficiency, regional pathology (helminthiasis, viral infections transmitted by blood-sucking insects), as well as ultraviolet radiation and background radiation;

3) differences in susceptibility and course of infection among the indigenous and immigrant populations, due to the length of residence in the North and their morphofunctional characteristics;

4) organizational and immunological problems of vaccine prevention due to low population density, which leads to an increase in the number of seronegative patients among vaccinated women;

5) the uniqueness of the gender, age and social structure of the population, forming non-immune groups and carriers of infection.

According to some data, during an epidemiological and immunological study of cytomegalovirus infection in mothers and newborns of the indigenous and alien population in the Far North, women who migrated from other regions of Russia showed a more frequent detection of cytomegalovirus in cells (30.8%) compared to aborigines ( 12.2%).

When studying specific immunity, complement-fixing antibodies are detected in 51.9% of women of the indigenous population and in 52.9% of the immigrant population during childbirth. At the same time, there is a lower rate of seropositive non-pregnant patients (35.3%) among the indigenous population and

a higher figure (38.1%) is among visiting women. Significant differences discovered by the authors (p<0,05) между небеременными и беременными пациентками позволяют говорить о значении геста-ционного процесса в реактивации цитомегаловируса у женщин.

Studies show that shedding of the herpes simplex virus increases in pregnant women during some winter and spring-summer months. The peak incidence of herpes infection in the winter is associated with a decrease in temperature, and in the summer - with an increase in solar activity and background radiation.

Influenza A viruses, as well as RNA and DNA respiratory viruses, can play a key role in disrupting the nature of the relationship in the “human - herpes simplex virus” system. Thus, during an epidemic of influenza A or the circulation of other pathogens, changes in the immune status of patients contribute to the activation of the herpes virus and its transition to an infectious form, causing a subclinical or clinical picture of the disease. For influenza A, as well as during detection of influenza outbreaks

B, parainfluenza types 1-3, rhinoscintial and adenovirus infections, patients are clinically diagnosed with herpes in the form of rashes on the lips, on the skin of the wings of the nose, on the cheeks, ears and skin of the eyelids, as well as on the mucous membrane of the oral cavity. Herpetic rashes in patients with influenza A appear on the lips and facial skin on the 3rd-4th day of the disease. Clinical signs of herpes are detected in 14-25% of all patients with influenza.

In the development of herpes infection, factors such as pathogen adsorption inhibitors and specific antiviral immunity are important. There are chemicals that can disrupt the establishment of contact between the herpes virus and the cytolemma of the somatic cell due to competition for various receptors that ensure the adsorption process of the pathogen.

LITERATURE

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S.Ya. Gaidamovich. M.: Medicine, 1982. T.2. S.".375-412.

2. Glinskikh N.P. Unknown epidemic: herpes (pathogenesis, diagnosis, clinic, treatment). Smolensk: Pharmagraphics, 1997. 162 p.

3. Dubov A.V. Adaptation of the human-virus system in the conditions of the Far North // Human adaptation in various climatic-geographical and industrial conditions: abstract. report III All-Union. conf. Novosibirsk, 1981. T.Z. P.98-99.

4. Features of the epidemiology of infectious diseases in the Asian Far North / Egorov I.Ya. [and others] // Epid. and inf. diseases. 1999. No. 3. P.60-62.

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6. Malevich Yu.K., Kolomiets A.G. Pathogenesis of perinatal herpetic infection // Issues. security mat. and children 1987. T.32, No. 1. P.64-68.

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Received 10/11/2010

Mikhail Timofeevich Lutsenko, head of the laboratory, 675000, Blagoveshchensk, st. Kalinina, 22;

Mikhail T. Lutsenko, 22, Kalinin Str., Blagoveschensk, 675000;

HSV type 2 (Herpes simplex virus type 2 - HSV-2), or human herpesvirus HSV-2;
3. Chickenpox virus - herpes zoster (Varicella-zoster virus - VZV), or human herpesvirus HHV-3;
4. Epstein-Barr virus - EBV (Epstein-Barr virus, EBV), or human herpesvirus HHV-4;
5. Cytomegapovirus - CMV, or human herpesvirus HHV-5;
6. Human herpesvirus type b - HHV-6 (Human herpesvirus - HHV-6), or human herpesvirus HHV-b;
7. Human herpesvirus type 7 - HHV-7 (Human herpesvirus - HHV-7);
8. Human herpesvirus type 8 - HHV-8 (Human herpesvirus - HHV-8).

“The subfamily also includes the old world monkey B virus, which causes fatal neurological damage.

Rice. 4.26.

Rice. 4.28

Reproduction. After attachment to cell receptors, the virion envelope fuses with the cell membrane (1, 2). The released nucleocapsid (3) delivers viral DNA into the cell nucleus. Next, part of the viral genome is transcribed (using cellular DNA-dependent RNA polymerase); the resulting mRNAs (4) penetrate into the cytoplasm where the synthesis (translation) of the earliest alpha proteins (I), which have regulatory activity, occurs. Then early beta proteins (P) are synthesized - enzymes, including DNA-dependent DNA polymerase and thymidine kinase, involved in the replication of the genomic DNA of the virus. Late gamma proteins (L) are structural proteins, including capsid and glycoproteins (A, B, C, D, E, F, G, X). Glycoproteins are diffusely adjacent to the nuclear envelope (5). The nascent capsid (6) is filled with viral DNA and buds through modified nuclear envelope membranes (8). Moving through the Golgi apparatus, virions are transported through the cytoplasm and exit the cell by exocytosis (9) or cell lysis (10).

Clinically significant members of the family

The herpes simplex virus belongs to the family Herpesviridae, genus Simplexvirus. Causes herpes simplex, characterized by vesicular rashes on the skin, mucous membranes, damage to the central nervous system and internal organs, as well as lifelong carriage (persistence) and relapses of the disease.
The herpes simplex virus includes two types: HSV-1 and HSV-2; distributed everywhere, affects most of the world's population and exists in the body in latent form until reactivation.
HSV-1 primarily affects the mouth, eyes, and central nervous system, while HSV-2 affects the genitals, which is why it is called the genital strain.
Structure. The structure of HSV is similar to other herpes viruses. The HSV genome encodes about 80 proteins necessary for virus reproduction, virus interaction with body cells and the immune response. HSV encodes 11 glycoproteins, which are attachment proteins (gB, dS, gD, dN), fusion proteins (dB), structural proteins, immune “evasion” proteins (dS, dE, gl), etc. For example, the C3 component of complement binds to dS, and the Fc fragment of IgG binds to the gE/gl complex, masking the virus and virus-infected cells. There are glycoproteins that have common antigenic determinants (gB, gD) for HSV-1 and HSV-2.

Rice. 4.27. Electron diffraction pattern of an ultrathin section of the Epstein-Barr virus (according to A.F. Bykovsky)

Rice. 4.29. Electron diffraction pattern of an ultrathin section of HSV: 1 - shell; 2 - capsid; 3 - tegument. (According to A.F. Bykovsky and others)

Rice. 4.30.

Microbiological diagnostics. The contents of herpetic vesicles, saliva, scrapings from the cornea, blood, semen, urine, cerebrospinal fluid and brain, in case of death, are examined. In smears stained according to Romanovsky-Giemsa, syncytium is observed - giant multinucleated cells with enlarged cytoplasm and intranuclear Cowdry inclusions. They infect a culture of HeLa cells, Hep-2, and human embryonic fibroblasts. Intracerebral infection of chicken embryos or suckling mice, which develop encephalitis, is carried out. Virus identification: RIF and ELISA using monoclonal antibodies; PCR. Serodiagnosis is carried out using RSK, RIF, ELISA and PH based on an increase in antibody titer (IgM, IgG).

Specific prevention of recurrent herpes carried out during the period of remission by repeated administration of an inactivated cultural herpetic vaccine.