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Herpesviridae
DR.HAMISI MKINDI,MD.
TO DOWNLOAD CONTACT: hermyc@live.com
Introduction
• Leading cause of human viral disease.
• 25 viruses in the family Herpesviridae
• Three sub-families
• Eight are known to infect Human
• Infection remains for life
Virology
• Herpes viruses are enveloped viruses
• Capsomere of about 100-200 nm
• Icosahedral nucleocapsid
• Contains 162 capsomeres
• Double stranded DNA
Replication
Replication
• RNA transcription: cellular enzyme (DNA-
dependent RNA polymerase I).
• DNA synthesis: Herpes viruses encode
their own DNA-dependent DNA
polymerase. Other enzyme (such as
thymidine kinase)
• Assembly: Nucleocapsids are assembled
in the nucleus.
Proteins
• Alpha proteins: These are the immediate-
early proteins.
• Beta proteins. Involved also in DNA
replication (DNA polymerase and
transcription factors).
• Gamma proteins. Late proteins are
structural components of the virus.
Herpes simplex Virus (HSV)
• HSV-1
• HSV-2
Pathogenesis
• Transmission: Close contact
• Infect epithelial mucosal cells or
lymphocytes: receptors gB and gD
• Travels up peripheral nerves to a ganglion
• Herpes simplex 1 and 2 can infect both
humans and other animals
•
Immune escape
• gC, gE and gI).
• gC which binds complement C3 and Fc
Immune response
• Neutralizing IgG may be present
throughout life
• Complement-mediated lysis of infected
cells
• Cytotoxic T-lymphocytes, NK cells and
macrophages in acute and in recurrent
infections
Reactivation
• Immunosuppression
• Stress
• Trauma
• Ultraviolet radiation
• Fever
Clinical diseases
• Oral herpes - Cold sores
• Herpes keratitis
• Herpes whitlow
• Neonatal herpes
• Genital herpes
• HSV Encephalitis
• HSV meningitis
Varicella-Zoster Virus
• Human Herpes Virus-3
• Two diseases: Chickenpox (Varicella) and
shingles (Zoster)
Pathogenesis and Immnunity
• Inhalation
• Replicates in the mucosa of respiratory
tract.
• Dissemination lymphatics and blood
stream
• Multiplication: Endothelial cells, monocytes
• Multiplication in the epithelial cells Lead to
rashes
Cont
• Virus ascend the axons of sensory nerves.
• Localized on sensory ganglia
• It becomes latent for life time.
• Infection is controlled by T cell mediated
immunity
• Reactivation: Shingles
• 10-20% of previously infected.
Chickenpox (Varicella)
• More than 90% of US have antibodies
• Highly infectious
• Lesions on the trunk, spread to heads and
limbs
• Itchy lesions
• 1 in 1000 get neurological complication
Herpes Zoster
• Results from reactivation of virus
• Vesicles are unilateral (confined to the
area innervated by sensory ganglion
(Zoster, girdle)
• Trunk, face
Laboratory diagnosis
• Clinical
• Specimen: smears from the base of early
skin lesion, Vesicle fluid
Monoclonal fluorescent antibody
EIA
PCR
Culture on Human lung embryonic
fibroblast, CPE after 2 weeks or more.
Treatment and control
• Acyclovir ( prevent dissemination in
immunosuppressed patients.
• Varicella immunoglobulin
• Vaccine There is a live attenuated
vaccine.
Epstein- Barr Virus
• Causative agent:
Burkitt's lymphoma,
Nasal pharyngeal carcinoma
Infectious mononucleosis
Infectious Mononucleosis
• An acute d’se x’zed by fever and swollen
lymph nodes and abnormal increase of
mononuclear leucocytes or monocytes in
the bloodstream;not highly
contagious;believed to be transmitted
through kissing
Receptors for the virus
• Infects cell types that express the receptor
for complement C3d component (CR2 or
CD21). T
epithelial cells (oro- and naso-pharynx)
B lymphocytes.
(cellular tropism)
Pathogenesis
• Transformation of B cells
Genome persist as plasmid
EBNA-2 is expressed
It immortalizes the B cell
Depression of Cell mediated immunity (IL-
10 analog)
• Burkitt's lymphoma
Translocation between chromosomes 8 and
14 brings c-myc near IG promoter
Infectious mononucleosis
Glandular fever
• Presents 1-2 months of infection.
• Characterized by
malaise,
lymphadenopathy,
tonsillitis
enlarged spleen and liver.
fever
Lab Diagnosis
• Heterophile antibodies (IgM agglutinate
sheep RBC
• EBV specific antibodies
CMV
• Largest genome of herpes viruses and
appears only to replicate in human cells.
• Form multinucleated cells (syncytia)
• Latent infection : T lymphocytes and
stromal cells of the bone marrow.
• There is only one serotype
Pathogenesis
• Once infected individual carry it for life.
• Intermittently shed in Saliva, urine, semen
and cervical secretions, breast milk.
• Reactivation occurs:
Pregnancy
Immunosuppression (AIDS
• Pathogenesis and latency mechanisms
are not known
Congenital disease
• During a primary infection of the mother,
congenital abnormalities
microcephaly,
rash,
brain calcification
hepatosplenomegaly.
hearing loss
Retardation..
Cont
• Perinatal infection of the newborn or
infants
•
Disease in immunosuppressed patients
Organ transplant
Immunosuppressive disease (e.g. AIDS),
• cytomegalovirus can be a major problem.
cytomegalovirus-retinitis 15% of AIDS.,
interstitial pneumonia,
colitis,
esophagitis
encephalitis.
Lab Diagnosis
• Culture
• Fluorescent stain
• PCR
• DNA hybridization
• EIA
HHV 6
• Found worldwide and is
• Found in the saliva of the majority of adults
(>90%)
• All children by the age of two are infected and
the infection is life-long
• Replicates in
– B and T lymphocytes,
– megakaryocytes,
– glioblastoma cell
– oropharynx.
latent infection in T cells
Clinical diseases
• Rashes
• Lymphadenopathy
• Encephalopathy
HHV-7
• Binds to the CD4 antigen
• Replicates in T4 (CD4+) cells
• Found in the saliva of the majority of the
adult population (>75%).
• Infection as children.
• Cases of exanthema subitum
HHV-8
• Subfamily: Gammaherpesvirinae
• Identified in 1994
• 140kbp
• Transmission Sexually, or non sexual route
• Molecular type: A, B,C 3% nucleotide variability
• K1 gene ecodes transmembrane glycosylated
protein

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13.Herpesviridae.ppt

  • 2. Introduction • Leading cause of human viral disease. • 25 viruses in the family Herpesviridae • Three sub-families • Eight are known to infect Human • Infection remains for life
  • 3.
  • 4.
  • 5.
  • 6. Virology • Herpes viruses are enveloped viruses • Capsomere of about 100-200 nm • Icosahedral nucleocapsid • Contains 162 capsomeres • Double stranded DNA
  • 8. Replication • RNA transcription: cellular enzyme (DNA- dependent RNA polymerase I). • DNA synthesis: Herpes viruses encode their own DNA-dependent DNA polymerase. Other enzyme (such as thymidine kinase) • Assembly: Nucleocapsids are assembled in the nucleus.
  • 9. Proteins • Alpha proteins: These are the immediate- early proteins. • Beta proteins. Involved also in DNA replication (DNA polymerase and transcription factors). • Gamma proteins. Late proteins are structural components of the virus.
  • 10. Herpes simplex Virus (HSV) • HSV-1 • HSV-2
  • 11. Pathogenesis • Transmission: Close contact • Infect epithelial mucosal cells or lymphocytes: receptors gB and gD • Travels up peripheral nerves to a ganglion • Herpes simplex 1 and 2 can infect both humans and other animals •
  • 12. Immune escape • gC, gE and gI). • gC which binds complement C3 and Fc
  • 13. Immune response • Neutralizing IgG may be present throughout life • Complement-mediated lysis of infected cells • Cytotoxic T-lymphocytes, NK cells and macrophages in acute and in recurrent infections
  • 14. Reactivation • Immunosuppression • Stress • Trauma • Ultraviolet radiation • Fever
  • 15. Clinical diseases • Oral herpes - Cold sores • Herpes keratitis • Herpes whitlow • Neonatal herpes • Genital herpes • HSV Encephalitis • HSV meningitis
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21. Varicella-Zoster Virus • Human Herpes Virus-3 • Two diseases: Chickenpox (Varicella) and shingles (Zoster)
  • 22. Pathogenesis and Immnunity • Inhalation • Replicates in the mucosa of respiratory tract. • Dissemination lymphatics and blood stream • Multiplication: Endothelial cells, monocytes • Multiplication in the epithelial cells Lead to rashes
  • 23. Cont • Virus ascend the axons of sensory nerves. • Localized on sensory ganglia • It becomes latent for life time. • Infection is controlled by T cell mediated immunity • Reactivation: Shingles • 10-20% of previously infected.
  • 24. Chickenpox (Varicella) • More than 90% of US have antibodies • Highly infectious • Lesions on the trunk, spread to heads and limbs • Itchy lesions • 1 in 1000 get neurological complication
  • 25. Herpes Zoster • Results from reactivation of virus • Vesicles are unilateral (confined to the area innervated by sensory ganglion (Zoster, girdle) • Trunk, face
  • 26.
  • 27. Laboratory diagnosis • Clinical • Specimen: smears from the base of early skin lesion, Vesicle fluid Monoclonal fluorescent antibody EIA PCR Culture on Human lung embryonic fibroblast, CPE after 2 weeks or more.
  • 28. Treatment and control • Acyclovir ( prevent dissemination in immunosuppressed patients. • Varicella immunoglobulin • Vaccine There is a live attenuated vaccine.
  • 29. Epstein- Barr Virus • Causative agent: Burkitt's lymphoma, Nasal pharyngeal carcinoma Infectious mononucleosis
  • 30. Infectious Mononucleosis • An acute d’se x’zed by fever and swollen lymph nodes and abnormal increase of mononuclear leucocytes or monocytes in the bloodstream;not highly contagious;believed to be transmitted through kissing
  • 31. Receptors for the virus • Infects cell types that express the receptor for complement C3d component (CR2 or CD21). T epithelial cells (oro- and naso-pharynx) B lymphocytes. (cellular tropism)
  • 32. Pathogenesis • Transformation of B cells Genome persist as plasmid EBNA-2 is expressed It immortalizes the B cell Depression of Cell mediated immunity (IL- 10 analog) • Burkitt's lymphoma Translocation between chromosomes 8 and 14 brings c-myc near IG promoter
  • 33. Infectious mononucleosis Glandular fever • Presents 1-2 months of infection. • Characterized by malaise, lymphadenopathy, tonsillitis enlarged spleen and liver. fever
  • 34. Lab Diagnosis • Heterophile antibodies (IgM agglutinate sheep RBC • EBV specific antibodies
  • 35. CMV • Largest genome of herpes viruses and appears only to replicate in human cells. • Form multinucleated cells (syncytia) • Latent infection : T lymphocytes and stromal cells of the bone marrow. • There is only one serotype
  • 36. Pathogenesis • Once infected individual carry it for life. • Intermittently shed in Saliva, urine, semen and cervical secretions, breast milk. • Reactivation occurs: Pregnancy Immunosuppression (AIDS • Pathogenesis and latency mechanisms are not known
  • 37. Congenital disease • During a primary infection of the mother, congenital abnormalities microcephaly, rash, brain calcification hepatosplenomegaly. hearing loss Retardation..
  • 38. Cont • Perinatal infection of the newborn or infants •
  • 39. Disease in immunosuppressed patients Organ transplant Immunosuppressive disease (e.g. AIDS), • cytomegalovirus can be a major problem. cytomegalovirus-retinitis 15% of AIDS., interstitial pneumonia, colitis, esophagitis encephalitis.
  • 40. Lab Diagnosis • Culture • Fluorescent stain • PCR • DNA hybridization • EIA
  • 41. HHV 6 • Found worldwide and is • Found in the saliva of the majority of adults (>90%) • All children by the age of two are infected and the infection is life-long • Replicates in – B and T lymphocytes, – megakaryocytes, – glioblastoma cell – oropharynx. latent infection in T cells
  • 42. Clinical diseases • Rashes • Lymphadenopathy • Encephalopathy
  • 43. HHV-7 • Binds to the CD4 antigen • Replicates in T4 (CD4+) cells • Found in the saliva of the majority of the adult population (>75%). • Infection as children. • Cases of exanthema subitum
  • 44. HHV-8 • Subfamily: Gammaherpesvirinae • Identified in 1994 • 140kbp • Transmission Sexually, or non sexual route • Molecular type: A, B,C 3% nucleotide variability • K1 gene ecodes transmembrane glycosylated protein