Herpes simplex virus. Morphology and structure of virions. biological properties. The pathogenesis of the disease in humans. Reproduction of herpes viruses. The replication cycle of herpesviruses. Poxviruses. Reproduction of poxviruses Morphology and structure of the herpes virus
Table of contents of the subject "Virology. Reproduction of viruses. Genetics of viruses.":1. Virology. History of virology. Chamberlain. RU. Pasteur. Ivanovsky.
2. Reproduction of viruses. Reproduction of +RNA viruses. Picornaviruses. reproduction of picornaviruses.
3. Togaviruses. Reproduction of togaviruses. Retroviruses. reproduction of retroviruses.
4. Reproduction of -RNA viruses. Reproduction of viruses with double-stranded RNA.
5. Reproduction of DNA viruses. Replication cycle of DNA-containing viruses. Reproduction of papovaviruses. Reproduction of adenoviruses.
7. Reproduction of the hepatitis B virus. Replication cycle of the hepatitis B virus.
8. Genetics of viruses. Characteristics of viral populations. Gene pool of viral populations.
9. Mutations of viruses. Spontaneous mutations of viruses. Induced mutations of viruses. Manifestation of viral mutations in the phenotype.
10. Genetic interactions between viruses. Recombination and redistribution of genes by viruses. Exchange of genome fragments by viruses. Antigenic shift.
The main differences in the reproductive cycle herpesviruses from other DNA viruses associated with a more complex structure of the genome. Adsorption of viruses on cells is carried out through specific receptors. After interaction with receptors, the viral envelope fuses with the cell membrane, and the nucleocapsid is released into the cytoplasm. The undressing (deproteinization) of the viral genome occurs at the nuclear membrane, and the viral DNA ends up in the nucleus of the host cell. Reproduction includes early and late stages, but they are not clearly distinguished.
Early stage of reproduction of herpesviruses. In the early stage, "early proteins" are synthesized, encoded by the proximal third of the DNA molecule. They exhibit regulatory properties, including activation of transcription of other regions of the viral genome encoding DNA polymerase and DNA-binding proteins.
Late stage of reproduction of herpesviruses. In the late stage, viral DNA polymerase induces replication of maternal DNA. As a result, DNA molecules of the daughter population are formed. Part of the daughter DNA is read by cellular polymerases, which causes the transcription of terminal genes encoding structural proteins (envelope proteins and spike glycoproteins).
Assembly of daughter populations of herpesviruses is carried out in the nucleus, where capsid proteins surround DNA molecules, forming nucleocapsids. The final stage of herpesvirus morphogenesis is the formation of a supercapsid on the inner surface of the nuclear membrane. Mature daughter populations bud from the modified nuclear membrane, are transported through the cytoplasm, and are released to the outside.
Poxviruses. Reproduction of poxviruses.
Poxviruses have the most complex reproductive cycle, while more than 100 different proteins that make up the virions are synthesized (the majority forms the outer shell). The reproduction of poxviruses is characterized by the following features.
DNA transcription begins before the complete deproteinization of the virus, since it is completely carried out by viral polymerases.
replication occurs only in the cytoplasm and is completely independent of cellular polymerases, since, unlike other viruses, poxviruses have their own DNA-dependent RNA polymerase, which ensures that more than half of the viral genome is read during the initial and early stages.
In the reproductive cycle There are three stages - initial, early and late.
Rice. 5-4. Replication cycle of DNA-containing viruses(on the example of the reproduction of the herpes virus). After adsorption (1), the virus enters the cell by fusion with the membrane (2). The nucleocapsid is transported to the nuclear envelope (3), and the viral DNA (vDNA) enters the cell nucleus, where its transcription by the cellular DNA-dependent RNA polymerase begins (4). The "early genes" are transcribed first. As a result of translation of the "early portion" of the viral genome, "early proteins" are synthesized (5), including regulatory, template, and viral polymerases. Viral polymerase penetrates into the cell genome (6), where it triggers the synthesis of DNA molecules of daughter populations (7). Part of the viral DNA (“late genes”) of daughter populations is transcribed by cellular RNA polymerase (8), which leads to the synthesis of “late proteins” (9) necessary for the assembly of daughter populations (10). The latter leave the nucleus, budding from its membrane (11), fragments of which they contain in their shell.
The initial stage of reproduction of poxviruses starts immediately after the undressing of the virus and the release of viral DNA into the cytoplasm.
Early stage of poxvirus reproduction. At this stage, approximately half of the viral DNA is transcribed. Enzymes encoded by "early genes" and involved in viral DNA replication are synthesized. In parallel, structural proteins are formed in a small amount.
Late stage of poxvirus reproduction coincides with the start of DNA replication (which switches transcription mechanisms to read the second half of the genome). Regulatory proteins block the translation of "early mRNA" and trigger the synthesis of late (structural) proteins. Virions are assembled only in the cytoplasm through membrane synthesis reactions. The release of mature populations is accompanied by cell lysis.
Microbiology: lecture notes Tkachenko Ksenia Viktorovna
2. Herpes virus
2. Herpes virus
The Herpesviridae family includes subfamilies:
1) a-herpesviruses (types I and II, herpes zoster);
2) b-herpesviruses;
3) g-aherpesviruses.
They belong to DNA viruses. DNA is double-stranded, linear. The genome consists of two fragments: long and short. The DNA strand is wound around a central protein culture. The capsid shell is built from simple proteins and has a cubic symmetry type. There is a supercapsid membrane (lipid membrane with a layer of glycoproteins), heterogeneous in structure, forms spiny processes.
Herpes viruses are relatively unstable at room temperature, heat-labile, and rapidly inactivated by solvents and detergents.
a-herpes type I causes aphthous stomatitis in early childhood, labial herpes, less often herpetic keratitis and encephalitis.
a-herpes type II causes genital herpes, neonatal herpes, is a predisposing factor for the development of cervical cancer.
Herpes zoster is the causative agent of shingles and chicken pox. This is a typical herpes virus infection. It is clinically manifested by the appearance of bubbles on the skin along the branches of the corresponding nerves. The disease is severe, but recovery is quick.
After an infection, lifelong immunity remains. However, relapses of the disease associated with the persistence of the virus in the nerve ganglia are possible.
After suffering a herpes virus disease, the virus persists for life in the nerve ganglia (often the trigeminal nerve). With a decrease in the body's defenses, a viral infection develops.
b-herpes (cytomegalovirus) during reproduction in culture cells causes cytopathic changes. It has an affinity for the cells of the salivary glands and kidneys, causing the formation of large multinuclear inclusions in them. With the development of the disease, viremia takes place, damage internal organs, bone marrow, CNS, the development of immunopathological diseases.
g-herpes virus (Epstein-Bar virus) causes infectious mononucleosis. It may be a predisposing factor in the development of tumors.
Diagnostics:
1. a-herpes virus:
1) identification of characteristic multinucleated giant cells with inclusion bodies in scrapings from the affected area;
2) cultivation in chicken embryos;
3) biological sample;
4) serological studies (RSK, ELISA);
5) method of direct immunofluorescence with monoclonal antigens.
2. b-herpes virus:
1) detection of large cytomegalovirus cells in urine and saliva;
2) cultivation in the culture of human embryonic fibroblasts;
3) serological examination (RSK);
4) immunofluorescence.
3. g-herpes virus:
1) virus isolation in fibroblast culture;
2) microscopy of smears of urine sediment, saliva to identify typical giant cells;
3) serological methods (RSK, RPGA and RN).
1) antiviral drugs (acyclovir);
2) interferon.
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n Herpes viruses (from the Greek. herpes - creeping) - DNA containing n Every year 20 million people are infected with HSV
n alphaherpesvirinae a) human herpes simplex virus type I (HSV-1) HVV-1 b) human herpes simplex virus type II (HSV-2) HVV-2 c) varicella-zoster virus and herpes zoster HVV-3 genus Varicellovirus (VZV – Varicella-zoster virus)
n betaherpesvirinae a) cytomegalovirus (CMV) HHV-5 genus Cytomegalovirus b) infantile exanthema virus (affects children under 3 years old) HHV-6 c) chronic fatigue syndrome virus HHV-7
n gammaherpesvirinae a) Epstein-Barr virus (infectious mononucleosis and Burket's lymphoma) HHV-4 genus Lymphocryptovirus b) Kaposi's sarcoma-associated viruses HHV-8 genus Radinovirus
Properties of viruses: n size 150 - 210 nm, spherical or oval shape n DNA linear, 2-stranded n icosahedral protein capsid, consists of 162 capsomeres n glycolipoprotein shell with glycoprotein spikes n tegument is located between the capsid and the glycoprotein shell - these are proteins, enzymes needed for replication
Virus reproduction n Virus envelope attaches to target cell membrane receptors n Fusion and entry by receptor endocytosis n Released nucleocapsid enters the cell nucleus. Transcription occurs (DNA in i. RNA), then i-RNA penetrates into the cytoplasm
The reproduction of the virus n begins the synthesis of non-structural (synthesis regulators and enzymes) and structural proteins (capsid, HP). GPs are adjacent to the nuclear membrane n the formed capsid is filled with DNA and buds through the nuclear membrane into the cytoplasm n exit occurs (exocytosis or cell lysis)
General properties for viruses of the subfamily alphaherpesvirinae Rapid growth n Proliferate in the epithelium of the skin and mucous membranes n Have a cytolytic effect n Remain in neurons n Cause latent persistent infection n
General properties for viruses of the betaherpesvirinae subfamily Slow growth n Tropicity to the epithelium of the salivary glands, tonsils, kidneys, lymphocytes n Have cytomegalic (giant cells) and lymphoproliferative actions n
Common properties for viruses of the gammaherpesvirinae subfamily Grow only in lymphoblasts n Have a lymphoproliferative effect n Stimulate the reproduction of B-lymphocytes and cause persistent infection in them n Infect lymphoid tissue, salivary glands, epithelium of the mouth and pharynx n
Cultivation Depends on the specific virus chick embryo n cell lines (death, proliferation, nuclear inclusions - capsid residues detected by staining according to Romanovsky-Giemsa) n
Antigenic structure Two antigenic complexes - n Capsid - group-specific n Glycoprotein - species-specific, type-specific
General signs of herpesviruses n n n n Anthroponoses are not stable in the external environment. Polytropic - no strict organotropy Long-term persistence (chronic persistent infection with exacerbations) Immunosuppression (suppression of cellular immunity) Protection against the virus with the help of T-killers and macrophages that destroy the affected cells Antibodies do not have protective properties
Subfamily alphaherpesvirinae Discovered by Grüter in 1912 1. HSV type I (acute stomatitis, keratoconjunctivitis, pharyngitis, meningoencephalitis) up to 10% of the population are carriers of this virus. Ways of transmission - airborne, contact (mother-child up to 3 years), transplacental. 2. HSV type II (herpes in newborns, genital herpes, cervical cancer). n Ways of transmission - sexual, during childbirth, infection of the child
Herpes Simplex Virus n Negative stain n Color photo Both viruses have CPD - blistering (vesicular eruptions) Immunity Ig M - fresh infection, Ig G - chronic or persistent.
Subfamily alphaherpesvirinae HSV 1 and HSV 2 Laboratory diagnostics n Test material: scraping from vesicles, saliva, swab from the cervical canal in case of genital herpes, blood in case of generalization, cerebrospinal fluid in case of meningitis or encephalitis. n Express diagnostics. RIF, PCR, microscopy (intracellular inclusions and giant multinucleated cells)
Subfamily alphaherpesvirinae HSV 1 and HSV 2 Laboratory diagnostics n Virological method - chicken embryo - CAO (plaques), infection of mice into the brain (encephalitis), rabbits into the cornea of the eye (keratitis), culture of rabbit kidney cells (giant cells with intranuclear inclusions) Identification by RN, RSK, ELISA n Serodiagnosis by ELISA (IG M, G)
Subfamily alphaherpesvirinae HSV 1 and HSV 2 Specific relapse prevention: Herpes therapeutic culture-inactivated vaccine (reduces relapse rate but does not cure). n Treatment: virolex, acyclovir, famvir. n
Subfamily alphaherpesvirinae 3. n n Varicella-zoster virus (VZV) or GVV-3 (chickenpox and shingles) discovered by Arago (Brazilian doctor) in 1911 Chickenpox has an epidemic distribution
Subfamily alphaherpesvirinae Virus Varicella-zoster Pathogenesis Primary reproduction in the mucous membrane of the upper respiratory tract (incubation period - 10-15 days). Viremia Secondary reproduction - in the epithelium of the mucous membranes and skin (cytopathic effect)
Subfamily alphaherpesvirinae Virus Varicella-zoster n Formation of a bladder with serous fluid (vesicle) n Suppuration (pustule) is possible n Scar formation (pockmark) There is constant underseeding from reproduction sites, there can be up to 5 or more attacks, and the patient can see all the elements of the rash. In debilitated patients - bullous form (huge blisters), hemorrhagic form and gangrenous form.
Subfamily alphaherpesvirinae Virus Varicella-zoster Epidemiology n 100% contagiousness n Way of transmission - airborne, can be contact (rarely, because it is not very resistant) n Susceptible group - adults and children in the absence of immunity
Subfamily alphaherpesvirinae Virus Varicella-zoster Laboratory diagnostics Test material - nasopharyngeal lavage and discharge of vesicles n Express diagnostics - ELISA n Virological - culture of human embryonic fibroblasts (HRC). n Serodiagnosis - RSK, RTGA, ELISA.
Alphaherpesvirinae subfamily Varicella-zoster virus Specific prophylaxis Live attenuated vaccines Okavax (Japan), Varilrix (England) Human immunoglobulin against convalescents n Treatment - interferon, leukinferon, virolex n
Subfamily betaherpesvirinae 1. Cytomegalovirus infection (HVV 5) n According to WHO, 1-2% of children are born with this infection, by the age of 1 year, 20% of children have antibodies, by 30-50 years - 100% of antibodies n Identified in 1956 in the USA by Smith and Rod n Morphology - large sizes of DNA, changes the rate of cell growth, with the formation of giant multinucleated cells with inclusions in the nucleus
Subfamily betaherpesvirinae n Pathogenesis Reproduction in leukocytes and macrophages with long persistence n Epitheliotropism (salivary glands and kidneys) n Formation of infiltrates that are replaced by fibrous tissue
Subfamily betaherpesvirinae n n Clinical features Congenital CMV - when infected in early pregnancy, the fetus dies or birth defects. In the later stages - loss of vision, hearing, etc. Acquired CMV - acute (in young children, at the time of birth) or chronic infection (hepatolienal syndrome, kidney damage) In the later stages - asymptomatic infection with the formation of antibodies
Subfamily betaherpesvirinae Epidemiology n Source of infection - patients or virus carriers (viruses are found in all biological fluids) n Ways of transmission - transplacental, through amniotic fluid, contact, airborne, sexual
Subfamily betaherpesvirinae Laboratory diagnostics - in urine and saliva of cytomegalocellular cells n Virological method - culture of human embryonic fibroblasts (HRC, RN). n Serological method - ELISA, separately antibodies M and G, M - fresh infection.
Subfamily betaherpesvirinae n n Specific prophylaxis No vaccine yet Treatment - specific immunoglobulin - cytotect, used to treat pregnant women and newborns
Subfamily betaherpesvirinae 2. Infant exanthema virus HHV-6 n Discovered in 1986. Halo n T-lymphotropic virus - exanthema in infants with a sudden rise in temperature to 40 ° C. With and the same recession on the background of a rash.
Subfamily betaherpesvirinae 3. Chronic fatigue syndrome virus HHV-7 n Discovered by Frenkel in 1990 n T-lymphotropic virus - causes chronic fatigue syndrome (subfebrile arthralgia, weakness)
Subfamily gammaherpesvirinae 1. Epstein-Barr virus (EBV or HHV-4) was discovered in 1964 and causes infectious mononucleosis. n Described by Filatov more than 100 years ago. n Can cause malignant diseases - Burkitt's lymphoma (a tumor of the upper jaw in young Africans) when tropical conditions and Plasmodium malaria or nasopharyngeal carcinoma with recurrent mumps play a role. n May have B-cell leukemia.
Subfamily gammaherpesvirinae Cultivation B-lymphocytes (the virus causes them to proliferate, there is no CPP) n Antigens Capsid Nuclear Early membranous Significant for serodiagnosis. Ig G are produced primarily to capsid and early membrane hypertension n
Subfamily gammaherpesvirinae n Pathogenesis. Infection of the immune system. primary reproduction (mucosa of the oral cavity and nasopharynx) secondary reproduction occurs in B-lymphocytes, which leads to hyperplasia of the lymphoid tissue of the nasopharynx, polylymphadenopathy, hepatosplenomegaly May be self-healing Immunodeficiency may lead to the development of Burkitt's lymphoma (a malignant tumor consisting of B-lymphocytes, mainly in the brain )
Subfamily gammaherpesvirinae n Epidemiology. The disease is not contagious. Source - patients and virus carriers Ways of infection transmission - airborne, contact-household (with a kiss), transplacental (during childbirth) EBV was found in saliva, cervical secretion Mostly men from 14 to 29 years old get sick
Subfamily gammaherpesvirinae Laboratory diagnostics. n Express diagnostics. PCR for the detection of DNA in various biological fluids. ELISA. n Serodiagnostics. ELISA for the detection of antibodies (Ig. M to capsid AG - fresh infection) Specific prophylaxis. Absent
Herpes simplex virus Type 1 (HSV-1) Herpes simplex virus Type 2 (HSV-2) Epstein Barr virus (EBV) Cytomegalovirus (CMV) Varicella Zoster Virus (VZV) Human herpes virus 6 (exanthum subitum) or roseola infantum) Human herpes virus 8 (Kaposi's sarcoma-associate herpes virus)
n n n TABLE 2 - Properties of Herpes viruses Human herpes type Name Sub Family Target cell type Latency Transmission 1 Herpes simplex-1 (HSV-1) Alphaherpesvirinae Mucoepithelia Neuron Close contact 2 Herpes simplex-2 (HSV-2) Alphaherpesvirinae Mucoepithelia Neuron Close contact usually sexual 3 Varicella Zoster virus (VSV) Alphaherpesvirinae Mucoepithelia Neuron Contact or respiratory route 4 Epstein-Barr Virus (EBV) Gammaherpesvirinae B lymphocyte, epithelia B lymphocytes Saliva 5 Cytomegalovirus (CMV) Betaherpesvirinae Epithelia, monocytes, lymphocytes Monocytes, lymphocytes and possibly others Contact, blood transfusions, transplantation, congenital 6 Herpes lymphotropic virus Betaherpesvirinae T lymphocytes and others Contact, respiratory route 7 Human herpes virus-7 (HHV-7) Betaherpesvirinae T lymphocytes and others Unknown 8 Human herpes virus-8 (HHV-8) Kaposi's sarcoma-associated herpes virus (KSHV) Gammaherpesvirinae Endothelial cells Exchange of body fluids?
