Understanding of Pathogenesis of herpes infection

Pathogenesis of herpes infection
Pathogenesis of Herpesvirus infections

Pathogenesis of herpes infection

Study of the pathogenesis of herpes infections has shown that there may be various forms of interaction between virus and host in the body depending on the length of stay of the pathogen in the latter. Firstly, in connection with the little presence of virus in the infectious process can proceed in either acute (short incubation period with the subsequent development of characteristic symptoms) or inapparent (asymptomatic) form.

The second type of interaction is due to prolonged persistence of virus in the body and manifests itself in three main forms of infection: latent (asymptomatic persistence of the pathogen, at which violated a complete cycle of virus reproduction, and it is in the host cells as subvirusnyh structures; believe that can happen reproduction of the mature virus, with release it to the external environment (Zuev VA, 1988) or chronic (persistence of the virus manifested clinical symptoms of the disease for a long time).

Perhaps the development of a slow virus infection, which is characterized by long-term (months or years) incubation period followed by a slow pro gradient course, with the development of severe clinical symptoms and the patient's death. It should be borne in mind that the form of a short-term and long-term (persistence), the stay of the virus in the body are often closely linked - one form of infection goes into another (Zuev VA, 1979.1988).

Reproduction of herpesvirus in sensitive cells - a complicated process that takes place with the participation of many virions, cellular, and virusindutsiruemyh virusmodifitsirovannyh enzymes.

The main stages of herpes infection are the primary infection of the skin and mucosal colonization and acute infection of ganglia with the subsequent establishment latency, where only the viral DNA, located in the nuclei of neurons, indicates the presence of disease. At the end of the acute phase of infection, free herpes simplex virus (HSV) is no longer recognized in the sensitive ganglia. Mechanisms governing the transition from the acute phase of infection when the virus cannot be found in gomogevatah ganglion, not yet defined. This change is parallel to the development of immune factors: the host immune response reduces virus replication in the skin, removes the signal of ganglion cells become nepermiseivnyyaga - established latent infection.

Detection of herpes virus in the ganglia of people who have had past infection with HSV said d reactivation of infection which can occur as asymptomatic and the development of lesions of mucous membranes and skin.

In humans, asymptomatic, as well as symptomatic recurrence was observed after aschkroeeyrohirur-logical interventions on the trigeminal nerve. Reactivation of HSV is often also seen in individuals receiving immunodep-ressanty (such as piklofosfamid), for example, after organ transplantation or UV irradiation, activating effect of these and other factors are inextricably linked with the violation of detention in a cell-tsnkloadenoziimo nofosfat a (cAMP) whose role is great in the implementation of various intracellular processes.

In HSV-infected cells dramatically reduces the amount of cAMP. The imbalance between the cell and HSV under the influence of provoking factors leads to increased viral replication, which clinically manifested peaking. Then, between the virus and the cell establishes a new equilibrium, and formation of an active HSV terminated before until a provoking factor again does not violate this balance (Yaroslavl, VK et al., 1996).

There are two alternative theories (hypotheses) proposed to explain the mechanisms of persistence of herpes simplex, which allow for the development of recurrence based on a static or dynamic state of the virus (Roizman B., 1965). According to the static hypothesis, the herpes virus in cells of the paravertebral sensory ganglia in integrated or free unproductive state. Under the influence of the starting factor of the virus is activated and moves from the ganglion along the axon of peripheral nerve in the epithelial cells, where replicated. It is assumed that this is mainly due to the susceptibility of cells and weakening of the immunological control.

Dynamic hypothesis provides continuous replication of release from the ganglion of small amounts of herpes virus. Reaching the nerve Kozhitov HSV infections microfocus cause, restrain the mechanisms of protection that prevent recurrence or cuts their manifestations. On the development of relapses affect the local immunity, inhibition of which contributes to replication of the virus reached the skin.

A large number of experimental studies on animals helps to explore the various manifestations of herpetic infection of primary infection with HSV is the latent infection of spinal and cerebral ganglia where the virus comes from the atrium Endon-centrally, perineural intraaksonalnoili by Schwann cells. In addition to the neurogenic pathway of HSV infection, is of a great importance hematogenous route of spread as a result of the expressed zritropizma HSV, in consequence of which is an infection of new cells * K In addition, VPGtesno interacts with leukocytes and even platelets. In this case, there are gross chromosomal damage and large concentrations of HSV antigen in leukocytes.

Formation of latent infection is associated with structural changes in the viral genome. It is a fundamentally important provision was established methods of restriction analysis and blot hybridization with 32P-labeled viral DNA in virions compared to the reference DNA of HSV-1.

An important role in the pathogenesis of herpes infection is HSV excretion with saliva, urine, feces. The phenomenon of virus-Surya established in 1937 by LA Zilber.

Pathogenesis of CMV infection is not completely understood. The source of infection is a person who may become infected with CMV at different stages of life. It is shown that CMV infects the cells of various organs and systems, long-term persists in the body, and periodically released into the environment. Mechanism of development of CMV infection depends on many factors - in particular, are important ways of contamination, the individual (genetic) features of microorganism, the immune system at the time of infection. Infection with cytomegalovirus process is realized in the form of either an asymptomatic latent infection or symptomatic localized or generalized forms.

Gateway for CMV in the ant-e and intrapartum periods can damage the placenta, fetal membranes and the outer integument of the fetus, respiratory and digestive tract. The latter two pathways of virus observed in the postnatal period. Noted that pregnant women with latent infection fetus are affected is not always the case. To do this, the aggravation of the disease in the mother with the development of viremia and subsequent infection of the fetus. The probability of hitting a child would be significantly higher during primary infection during pregnancy. During phase viremia in the absence of antibodies in the mother (and hence the fetus) transmission of the virus to the fetus is carried out much easier than in the resistant organism previously (before pregnancy) an infected woman.

As noted above, the gateway CMV infection in children and adults may be the upper respiratory tract, allows the possibility of alimentary infection. We can assume that in these instances, the virus is embedded in the mucous membranes of the digestive tract. Any local changes to the site entrance gate of infection were observed. The virus has a distinct tissue tropism of salivary glands, with a localized form, it is found only in the tissues of the salivary glands.

Penetrated the blood of CMV in leukocytes and reproduced in the cells of a monocyte-macrophage system (MMS) or persists in the lymphoid organs. Established that penetrated into the cells MMS virus can cause them abortive infection, accompanied by expression of viral antigens such as early and late stages of the subsequent blockade of the replication agent. In experiments in vitro against abortive infection detected depression of the phagocytic, oxidative and bactericidal activity of macrophages, as well as the loss of Fc-receptors. True, there are few reports that the entry of CMV into macrophages does not harm the listed functions, and sometimes even makes them.

In response to the introduction of CMV develops resistant alteration microorganism. The transition of latent CMV infection in symptomatic form is usually provoked by any pathological genetic (down) factors - for example, using kortikoeteroidov, intercurrent diseases, the appointment of cytostatics and another immunodepressant cent. With the development of congenital or acquired immunodeficiency depression, including a dramatic inhibition of the functions of natural killer cells (EC), viruses go into the liquid medium and spread by the bloodstream to various organs. CMV virions adsorb * Camping on cell membranes and penetrate into the cytoplasm by pinocytosis or viropeksisa inducing metamorphosis cytomegalic cells.

Particularly sensitive to CMV, as noted, have the epithelial cells of small ducts of the salivary glands, primarily the parotid. CMV is associated with blood leukocytes (lymphocytes, monocytes), not only well protected from the effects of circulating protivotsitome-galovirusnyh antibodies, but also capable of further reproduction. Preliminary interstitial infiltration initiates the proliferative activity of the epithelium, during which, apparently, and metamorphosis occurs cytomegalic cells.

In this connection, mention should be made a conjecture AP Samokhin (1987), whereby infection of the epithelium of salivary ducts are in the process of transepithelial migration of lymphocytes and histiocytes. Perhaps cytomegalic transformation of proliferating epithelial cells is carried out in the assimilation of infected products lymphocytic decay or auto-analysis, which is formed around the root in the epithelium of sensitized T-lymphocytes. RP Piano (1968) found in the brains of cytomegalic giant cells (SSC) with the nuclei of phagocytized cells. This kind of finding confirms the hypothesis.

In recent years, there is substantial evidence in favor of the fact that in chronic viral infections may be formed lifelong immunosuppression. This primarily relates to AIDS, which in most cases, die from secondary infections that develop in HIV-induced immune deficiency. Apparently, the list of viruses that cause long-term immunosup-Ress will increase, primarily due to pathogens that can persist for a long time in the cells of the immune system. In full, this applies to herpes simplex virus and cytomegalovirus CMV immunological reactions in very diverse and largely determine the course and outcome of infection.

With herpes zoster (OG) virus infection is realized by airborne droplets. The virus is carried by its attachment to receptors on the plasma membrane of the host cell. As a result of a merger with the cell membrane of the virus exhaust its shell and built into it proteins become part of the cell membrane and the capsid, containing the genetic material is released and penetrates into the cytoplasm, then moves to the nucleus. Per minute in the cage penetrates about 3000 viral particles.

Viral DNA is transcribed in the nucleus while listening messenger RNA produced from the transcripts occurs in the cytoplasm. Replication of viral DNA is carried out in the core, after which it connects to unripe nuklekapsida-mi. The ability of the virus to infect cells develops as the acquisition of Kalends shell by budding through the inner lamella of the nuclear membrane. The yield of virus particles is carried out by their transport to the cell surface via a modified endoplazmetichesky reticulum.

Multiplication of herpes simplex and herpes zoster occurs in polymorphonuclear leukocytes and monocytes that virus protection from the humoral immunity factors and creates a strong foundation for further dissemination (Ba-maternal JF et al., 1986). Virus OG (VOG) was also found in red blood cells, which produce inclusions.

Macrophages, peripheral blood, liver, spleen, sinus bone marrow, lymph nodes, pleural: and peritoneal cavity, connective tissue, the respiratory tract are capable, according to some authors, to absorb both free virus particles and particles associated with blood cells, but thus completely eliminate the FOG they cannot always, in connection with which conditions are created for persistent-tion of FOG (Kolomiets et al., 1992).

It is shown that more than half the cases of MG patients accounted for over 50 years. It is known that humoral immune responses are not crucial in the fight against recurrent OG and only partially protect against the exogenous virus. Risk of reagents FOG activation increases dramatically in persons with diseases or conditions involving the development of immunodeficiencies of various origins.

Six clinic OG pressing significance syndrome posts Turney neuralgia (PZN), pathogenesis of which remains undisclosed. Many authors point to a postinfectious im munooposredovanny mechanism of PZN, i.e., when FOG is not detected and is not a direct destructive effect on neurons and the pathological changes caused by body's immune response. Vnrusneytralizuyuschie antibodies to the envelope protein FOG in some cases cross-react with myelin basic protein shell that underlies postinfectious demyelination (Umansky K. et al., 1992). It is shown that PZN is insensitive to the antiviral therapy, but well stopped by using the opposite-vogerpeticheskih immunoglobulins directed action. It denies the involvement of the virus in the genesis of PZN and reaffirms the role immunooposredovannyh mechanisms. Osobeyayao poor prognosis is the inhibition of cell-mediated-GOVERNMENTAL immunological reactions since the risk increases significantly enhance the FOG. In particular, it is shown that the longer the normalization of T-cell immunity, the duration of acute pain zosternaya (Higa K.etaL, 1992).

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