bohomolets microbiology lecture #14

DNA virusesDNA viruses

AdenoviridaeAdenoviridae

Herpesviridae Herpesviridae

Family AdenoviridaeFamily Adenoviridae

Genus Genus Hosts Hosts Types Types Avi-Avi-adenovirus adenovirus

BirdBird 1414

Mast-Mast-adenovirus adenovirus

Human Human 4949

Monkey Monkey 2727

Mouse Mouse 22

Dog Dog 22

Pig Pig 44

Horse Horse 11

Neat cattleNeat cattle 1010

Adenoviruses Adenoviruses

DNA virusesDNA virusesGenome – double-stranded linear DNAGenome – double-stranded linear DNADNA consist of 30 genes DNA consist of 30 genes 10 structural proteins are known 10 structural proteins are known Nonenveloped Nonenveloped Icosahedral shapeIcosahedral shapeCubical type of symmetryCubical type of symmetrySize – approximately 80 nm in Size – approximately 80 nm in diameterdiameterCapsid consist of 252 capsomers (240 Capsid consist of 252 capsomers (240 hexons and 12 pentons on the tops)hexons and 12 pentons on the tops)Virion contain special protein-Virion contain special protein-hemagglutinins (fibers) protruding from hemagglutinins (fibers) protruding from each of the 12 vertices of the capsideach of the 12 vertices of the capsid

Viruses replicate in the nucleus, form Viruses replicate in the nucleus, form intranuclear inclusionsintranuclear inclusions

Scheme of adenovirus structureScheme of adenovirus structure

Capsid proteins

DNA

Adenovirus structureAdenovirus structure

Electron micrographs of adenovirus Electron micrographs of adenovirus particlesparticles

Electron micrographs of adenovirusElectron micrographs of adenovirus

Hole virions Hemagglutinins (fibers)

Electron micrographs of adenovirusElectron micrographs of adenovirus

Models of adenovirusModels of adenovirus

Events of adenovirus reproductionEvents of adenovirus reproduction

1.1. Attachment to the cell via fiberAttachment to the cell via fiber

2.2. Penetration by viropexis Penetration by viropexis

3.3. Uncoating Uncoating

4.4. Viral DNA moves to the nucleusViral DNA moves to the nucleus

5.5. Transcription of early genes by using host cell DNA-Transcription of early genes by using host cell DNA-depend RNA-polymerasedepend RNA-polymerase

6.6. Synthesis of early nonstructural proteins in the cytoplasmSynthesis of early nonstructural proteins in the cytoplasm

7.7. Replication of viral DNA in the cell nucleus Replication of viral DNA in the cell nucleus

8.8. Transcription of late mRNA and translation of late Transcription of late mRNA and translation of late structural proteinsstructural proteins

9.9. Assembly of virions in the nucleus Assembly of virions in the nucleus

10.10. The viruses are released by lysis of the cell The viruses are released by lysis of the cell

Routs of transmission:Routs of transmission: Aerosol dropletAerosol droplet

Fecal-oralFecal-oral

Direct inoculation of conjunctivasDirect inoculation of conjunctivas

Affected tissues:

• Respiratory tract (both upper and lower)

• Gastrointestinal tract

• Conjunctivas

• Genitourinary tract

Human diseases caused by Human diseases caused by adenovirusesadenoviruses

Diseases Diseases Serotype of Serotype of virus virus

Epidemic disease in childrenEpidemic disease in children 1, 2, 5, 61, 2, 5, 6

Pharyngitis, pharyngoconjunctival feverPharyngitis, pharyngoconjunctival fever 3, 4, 7, 143, 4, 7, 14

Acute respiratory diseaseAcute respiratory disease 4, 7 , 14, 214, 7 , 14, 21

ConjunctivitisConjunctivitis 2, 3, 5, 7, 212, 3, 5, 7, 21

Epidemic keratoconjunctivitisEpidemic keratoconjunctivitis 8, 19, 378, 19, 37

Hemorrhagic cystitisHemorrhagic cystitis 40, 4140, 41

Infantile gastroenteritis with nonbloody Infantile gastroenteritis with nonbloody diarrheadiarrhea

38, 40, 4138, 40, 41

Affection of CNS (meningitis, encephalitis)Affection of CNS (meningitis, encephalitis) 3, 7, 213, 7, 21

Affection of heart Affection of heart 22

Classification of adenoviruses Classification of adenoviruses according to their oncogenisityaccording to their oncogenisity

Class of Class of oncogenisity oncogenisity

Serotype of Serotype of virusvirus

А – А – highly highly oncogenic oncogenic

12, 18, 3112, 18, 31

В – В – lowly lowly oncogenic oncogenic

3, 7, 11, 14, 213, 7, 11, 14, 21

С – С – nononcogenic nononcogenic 1, 2, 5 і 61, 2, 5 і 6

Laboratory diagnosis of Laboratory diagnosis of adenoviral infectionsadenoviral infections

Rapid detectionRapid detection – – detection of viral antigens in detection of viral antigens in affected cells with immunofluorescens reactionaffected cells with immunofluorescens reaction

Virological methodVirological method – – isolation of viruses in cell isolation of viruses in cell culture and identificationculture and identification ( (CPE and serological tests CPE and serological tests – complement binding test, inhibition of hemagglutination – complement binding test, inhibition of hemagglutination

test, virus neutralization testtest, virus neutralization test))Serological diagnosticSerological diagnostic – – detection of a 4-fold or detection of a 4-fold or greater rise of antibody titer (complement binding test)greater rise of antibody titer (complement binding test)

GenodiagnosticGenodiagnostic –– polymerase chain reaction polymerase chain reaction

Adenoviral CPEAdenoviral CPE

Normal cells HeLa Swelling, rounding of cell, clustering

HerpesvirusesHerpesviruses

Division of herpesviruses according Division of herpesviruses according to hosts, susceptible to the virusesto hosts, susceptible to the viruses

Human Human – 8 – 8 species species PrimatesPrimates – 31 – 31 speciesspecies Other mammaliansOther mammalians – 31 – 31 speciesspecies BirdsBirds – 12 – 12 speciesspecies ReptilesReptiles– 6 – 6 speciesspecies

HerpesvirusesHerpesviruses

DNA virusesDNA virusesGenome – double-stranded linear DNAGenome – double-stranded linear DNADNA consist of approximately 80 genes DNA consist of approximately 80 genes that code 80 proteinsthat code 80 proteinsEnveloped Enveloped Icosahedral symmetry of nucleocapsidIcosahedral symmetry of nucleocapsidSize – 120-200 nm in diameterSize – 120-200 nm in diameterVirion does not contain a polymeraseVirion does not contain a polymeraseViruses replicate in the nucleus, form Viruses replicate in the nucleus, form intranuclear inclusionsintranuclear inclusionsHerpesviruses are the only viruses that Herpesviruses are the only viruses that obtain their envelopes by budding from obtain their envelopes by budding from the nuclear membranethe nuclear membraneHave tendency to cause latent Have tendency to cause latent infections with periodically recurrent infections with periodically recurrent acute conditions acute conditions

Structure of herpesvirus virionStructure of herpesvirus virion

Nucleocapsid

Tegument

Genome

Envelope

Glycoprotein spike І type

Glycoprotein spike ІI type

Kaposi’s sarcoma virusKaposi’s sarcoma virus

Genome

Capsid

Envelope

Tegument

Particles of herpesvirusesParticles of herpesviruses

Chickenpox virionsChickenpox virions

Herpesvirus virionsHerpesvirus virions

Herpesvirus virions without Herpesvirus virions without envelopeenvelope

Adherence of herpesviruses on the Adherence of herpesviruses on the cell membranecell membrane

Events of hepresvirus reproductionEvents of hepresvirus reproduction1. Penetration

2. Uncoating

3. Released viral DNA enters the nucleus

4. Transcription with host cell polymerase

5. Synthesis of early nunstructural protein in cytoplasm

6. Replication of viral DNA in the cell nucleus7. Synthesis and transportation of late structural proteins in the

nucleus7. Assembly of nucleocaplid

Strategy of herpesvirus DNA Strategy of herpesvirus DNA synthesissynthesis

Events of hepresvirus reproductionEvents of hepresvirus reproduction

8.

9.

10.

11.

12.

Release of herpesvirusesRelease of herpesviruses

Egression of herpesviruses from the nucleus

Egression of herpesviruses from the cell

Release of herpesviruses from the Release of herpesviruses from the infected cellinfected cell

Herpesviridae family classificationHerpesviridae family classification

Subfamilies:Subfamilies:

Alpha-herpesvirinae (Alpha-herpesvirinae (-herpesvirinae)-herpesvirinae)

Betha-herpesvirinae (Betha-herpesvirinae (-herpesvirinae)-herpesvirinae)

Gamma-herpesvirinae (Gamma-herpesvirinae (-herpesvirinae)-herpesvirinae)

Subfamily Subfamily Alpha-herpesvirinaeAlpha-herpesvirinae

Genus Genus Viruses Viruses Diseases Diseases

SimplexSimplex--virusvirus

Herpes simplex Herpes simplex virus typevirus type 1 1

(HSV-1)(HSV-1)

GingivostomatitisGingivostomatitis,, herpes herpes labialis, encephalitis, labialis, encephalitis, keratitis keratitis (ocular herpes)(ocular herpes)

Herpes simplex Herpes simplex virus typevirus type 2 2

(HSV-2)(HSV-2)

Herpes genitalis, encephalitis,Herpes genitalis, encephalitis, herpes of newbornherpes of newborn, , carcinoma carcinoma of cervixof cervix

VaricelloVaricello--virusvirus

Herpes zoster virus Herpes zoster virus (VZV)(VZV)

Varicella (chickenpox), herpes Varicella (chickenpox), herpes zoster (shingles)zoster (shingles)

Herpes simplex viruses 1, 2. Herpes simplex viruses 1, 2. Diseases and affected tissuesDiseases and affected tissues

Recurrent lesions of herpes labialis Recurrent lesions of herpes labialis (coldsore) (coldsore)

Herpesviral gingivostomatitisHerpesviral gingivostomatitis

Herpesviral gingivostomatitisHerpesviral gingivostomatitis

Neonatal herpes simplex Neonatal herpes simplex

Genital herpesGenital herpes

Vesicles

Chickenpox Chickenpox

Disseminated chicken pox lesions on the back

ChickenpoxChickenpox

Disseminated chicken pox lesions on the face

Chickenpox in the child Chickenpox in the child

Varicell-Zoster viral infectionsVaricell-Zoster viral infections

Chickenpox

Zoster (shingles)

Zoster (shingles)

Subfamily Subfamily Betha-herpesvirinaeBetha-herpesvirinae

Genus Genus Viruses Viruses Diseases Diseases

CytomeCytome--galovirusgalovirus

Cytomegalovirus (CMV)Cytomegalovirus (CMV) Cytomegalovirus Cytomegalovirus mononucleosis, mononucleosis, congenital CMV infection, congenital CMV infection, perinatal CMV infectionperinatal CMV infection

RoseoloRoseolo--virusvirus

Human herpesvirus-6 Human herpesvirus-6 (human T-limphotropic (human T-limphotropic virus)virus)

Acute febrile disease – Acute febrile disease – roseola, chronic roseola, chronic neurological diseaseneurological disease, , Hodgkin’s lymphoma, oral Hodgkin’s lymphoma, oral carcinoma, and T-cell carcinoma, and T-cell leukemialeukemia

Human herpesvirus-Human herpesvirus-77

CMV infection characteristicCMV infection characteristic Form of Form of infection infection

Trans-Trans-mission mission

Affected Affected objects objects

Features Features

Congenital Congenital CMV CMV infectioninfection

Trans-Trans-placental placental

Fetuses Fetuses Most infected newborns are born Most infected newborns are born without signs, a certain number without signs, a certain number exhibit enlarged liver and spleen, exhibit enlarged liver and spleen, capillary bleeding, microcephaly. capillary bleeding, microcephaly. In some cases death follows In some cases death follows within a few days or weeks. within a few days or weeks. Rarely - sequelae, including Rarely - sequelae, including hearing and visual disturbances hearing and visual disturbances and mental retardation. and mental retardation.

Perinatal Perinatal CMV CMV infectioninfection

During During exposure to exposure to the mother’s the mother’s vaginavagina

Newborns Newborns Chiefly asymptomatic, although Chiefly asymptomatic, although pneumonitis and a pneumonitis and a mononucleosis-like syndrome can mononucleosis-like syndrome can develop during the first 3 months develop during the first 3 months after birthafter birth

CMV mono-CMV mono-nucleosisnucleosis

Sexual Sexual contact, contact, blood blood transfusion transfusion

Immuno-Immuno-deficient deficient adults adults

Systemic disease with fever, Systemic disease with fever, severe diarrhea, hepatitis, severe diarrhea, hepatitis, pneumonia, and high mortality pneumonia, and high mortality

Cells infected by CMV Cells infected by CMV

Giant cell

Nucleus

Normal cell

Subfamily Subfamily Gamma-herpesvirinaeGamma-herpesvirinae

Genus Genus Viruses Viruses ПатологіяПатологія

LymphoLympho--cryptoviruscryptovirus

Epstein-Barr virus Epstein-Barr virus (EBV)(EBV)

Infectious mononucleosis, Infectious mononucleosis, Burkitt’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma.nasopharyngeal carcinoma.

Hairy leucoplakia (in AIDS Hairy leucoplakia (in AIDS patients)patients)

RhadinoRhadino--virusvirus

Human herpevirus Human herpevirus 88 (or Kaposi’s (or Kaposi’s sarcoma-associated sarcoma-associated herpesvirus)herpesvirus)

Kaposi’s sarcoma (a common Kaposi’s sarcoma (a common tumor of AIDS patients). tumor of AIDS patients).

Possible: multiple myeloma, Possible: multiple myeloma, cancer of the bloodcancer of the blood

Infectious mononucleosis Infectious mononucleosis

Angina when infectious mononucleosis

The symptoms of infectious mononucleosis are sore throat, high fever, and cervical lymphadenopathy, which develop after a long incubation period (30-50 days). Many patients also have a gray-white exudate in the pharynx

Burkitt’s lymphomaBurkitt’s lymphoma

Burkitt’s lymphoma is a B-cell malignancy that usually develops in the jaw and grossly swells the cheek.

African children 4 to 8 years old are usually affected

Nalopharyngeal carcinomaNalopharyngeal carcinoma

is a malignancy of epithelial cells that is a malignancy of epithelial cells that occurs in older Chinese and African menoccurs in older Chinese and African men

Blood smear of healthy humanBlood smear of healthy human

Blood smear of a patient with infectious Blood smear of a patient with infectious mononucleosis. Lymphocytes infected by EDVmononucleosis. Lymphocytes infected by EDV

Important features of common Important features of common herpesvirus infectionsherpesvirus infections

Virus Virus Primary Primary infectioninfection

Usual site Usual site of latencyof latency

Recurrent Recurrent infectioninfection

Route of Route of transmissiontransmission

HSV-1HSV-1 Gingivo-Gingivo-stomatitis stomatitis

Cranial Cranial sensory sensory ganglia ganglia

Herpes Herpes labialis, labialis, encephalitis, encephalitis, keratitiskeratitis

Via respiratory Via respiratory secretions and secretions and salivasaliva

HSV-2HSV-2 Herpes Herpes genitalis, genitalis, perinatal perinatal herpes herpes

Lumbar or Lumbar or sacral sacral sensory sensory gangliaganglia

Herpes Herpes genitalis genitalis

Sexual Sexual contact, contact, perinatal perinatal infectioninfection

VSVVSV Varicella Varicella Cranial or Cranial or thoracic thoracic sensory sensory gangliaganglia

Zoster Zoster Via respiratory Via respiratory secretions secretions

Important features of common Important features of common herpesvirus infectionsherpesvirus infections

Virus Virus Primary Primary infectioninfection

Usual Usual site of site of latencylatency

Recurrent Recurrent infectioninfection

Route of Route of transmissiontransmission

EBVEBV Infectious Infectious mono-mono-nucleosisnucleosis

B B lympho-lympho-cytes cytes

None None Via respiratory Via respiratory secretions and secretions and salivasaliva

CMVCMV Congenital Congenital infection, infection, mono-mono-nucleosis nucleosis

Uncertain Uncertain AsymptomAsymptomatic atic shedding shedding

Intrauterine Intrauterine infection, infection, transfusions, transfusions, sexual contact, sexual contact, via secretions (eg, via secretions (eg, saliva and urine)saliva and urine)

Common methods of laboratory Common methods of laboratory diagnosis of herpesviral infectionsdiagnosis of herpesviral infections

VirologicalVirological.. Isolation of viruses in the chicken Isolation of viruses in the chicken embryo and cell culture and following embryo and cell culture and following identification (detection of CPE and serological identification (detection of CPE and serological tests)tests)

Serological diagnosticSerological diagnostic – – detection of a 4-fold detection of a 4-fold or greater rise of antibody titer or greater rise of antibody titer

GenodiagnosticGenodiagnostic –– polymerase chain reactionpolymerase chain reaction

CPE caused by herpersiruses CPE caused by herpersiruses (syncytium formation)(syncytium formation)

Chicken embryos that infected by Chicken embryos that infected by herpesvirusesherpesviruses

Herpes simplex virus I type

Herpes simplex virus II type

Oncogenic DNA virusesOncogenic DNA viruses

Viruses that Viruses that cause cancer in cause cancer in human:human:

• PapillomaviridaePapillomaviridae• HerpesviridaeHerpesviridae• HepadnaviridaeHepadnaviridae

Viruses that cause cancer Viruses that cause cancer only in laboratory animal only in laboratory animal and in cell culture (not in and in cell culture (not in human):human):

AdenoviridaeAdenoviridaePolyomaviridaePolyomaviridae

Smallpox Smallpox

PoxvirusPoxvirus

Papillomaviruses Papillomaviruses