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Herpes viruses
=Herpesviridae
PROFESSOR
DR. SAAD HASAN
MOHAMMED ALI
Ph. D. VIROLOGY
2022
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
OBJECTIVES
1.. To preview the virological properties and
classification bases of the viral members of
Herpesviridae.
2..To list the range of human diseases caused by the
two types of Herpes simplex viruses.
3..To list the range of diagnostic methods to
differentiate between these two Herpes viral types.
4..To outline the control measures against Herpes
simplex viruses.
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
Classification
of Human
Herpesviruses
Examples
Subfamily Latent
Infections
Genus Official Name
("Human -
Herpesvirus")
Common
Name
Alpha Neurons Simplex
1
Herpes
simplex virus
type 1
2
Herpes
simplex virus
type 2
Varicello
3
Varicella-
zoster virus
Beta Glands, kidneys Cytomegalo
5 Cytomegalo
virus
Lymphoid tissue Roseolo
6
Human
herpesvirus 6
7
Human
herpesvirus 7
Gamma Lymphoid tissue Lymphocrypto
4
Epstein-Barr
virus
Rhadino
8
Kaposi sarcoma-
associated
herpesvirus
HERPESVIRUSES
HUMAN HRPESVIRUSES
 (100 Animal species).
( 8 Humans species).
Herpes Simplex Virus 1 and 2 (HHV1&2)
Varicella-Zoster Virus (HHV3)
Epstein-Barr Virus (HHV4)
Cytomegalovirus ( HHV5)
Human Herpesvirus 6 (HHV6)
Human Herpesvirus 7 (HHV7)
 Kaposi-Sarcoma Associated- Herpesvirus (KSHV) (HHV8)
Important Properties of
Herpesviruses
All= Morphologically Identical:
Icosahedral
Enveloped
Double stranded DNA genome.
DNA homology:
1-HSV 1 & 2 (50%)
2- HHV 6 & 7 (30-50%)
• Viral-Specific Enzymes= DNA
polymerase & Thymidine kinase
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
All= Morphologically
Identical
Different
herpes viruses
cannot be
distinguished
by electron
microscopy
Herpes virus particles from human vesicle
fluid (X 140,000). (JAWETZ 2019)
All =Characteristic
DISEASE:
Primary Infection
 Latent Infection
 Reactivation ((( frequently, but not
always, associated with Further
disease))).
Some HHVs=
Associated with Tumors and
Carcinomas
HSV-2 Cervical Carcinoma
CMV COLONIC CARCINOMA
PROSTATIC CARCINOMA
CERVICAL CARCINOMA
EBV Burkitt's lymphoma
Nasopharyngeal Carcinoma
HHV-8 Kaposi sarcoma in HIV.
Replication Cycle of Herpes Viruses
in General
1- Attachment =
Cellular Receptors = Heparan Sulphate
2- Fusion
3- Uncoating  Release of viral DNA
4- Transcription of Alpha genes  Alpha –proteins
(Cellular Preparation)
5-Transcription Beta genes  Beta- proteins =
(ENZYMES).
6- Viral DNA replication  Viral DNA .
7- Transcription Gamma genes  Gamma – proteins=
= Structural Proteins= Empty Capsids
Immediate early
Early
Late
Replication cycle(Continued…)
8- Packaging= DNA into capsids .
10- Accumulation of viral glycoproteins on
the nuclear membrane .
11- Get Envelope from nuclear membrane
.
12- VIRUSES GO OUT THE CELL
through {Endoplasmic Reticulum}
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
Herpes simplex viruses
Background:
Ubiquitous, host-adapted pathogens that
cause a wide variety of disease states.
 Two types exist: Both are closely related
but differ in epidemiology.
The term herpes is derived from the Greek
word “to creep or crawl”
Dates back to early Greek civilization,
approximately 2000 years ago, in reference to
the spreading nature of herpetic skin lesions.
‫مكان‬ ‫كل‬ ‫في‬ ‫موجودة‬
HERPES SIMPLEX VIRUSES
Pathogenesis
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
Latent infections for both herpes simplex and varicella-zoster viruses. Primary
infections occur in childhood or adolescence, followed by establishment of latent
virus in the cerebral or spinal ganglia. Later activation causes recurrent herpes
simplex or zoster. Recurrences are rare for zoster.
CMI=Cell-Mediated Immunity.
METHODS TO
DIFFERENTIATE
BETWEEN THE TWO
TYPES OF HERPES
SIMPLEX VIRUSES
CLINICAL BASES: According To
Anatomical Land mark of Waist ???
LESIONS ABOVE WAIST=TYPE 1
LESIONS BELOW WAIST=TYPE 2
Waist
HSV 1
HSV 2
1
HSV-1 is traditionally associated
with orofacial disease, whereas
HSV-2 is traditionally associated
with genital disease.
 Lesion location, however, is not
necessarily indicative of viral
type, as HSV-1 is associated with
genital infections more often
than HSV-2 in some unique
subpopulations.
Egg inoculation= Pocks size.
DNA Finger Printing=
‫فايروسات‬ ‫من‬ ‫نوع‬ ‫لكل‬ ‫النووي‬ ‫الحمض‬ ‫بصمة‬
• Different Bands Size of The Two Types of HSV-
DNA = by doing Restriction Enzymes analysis.
Different Serological Reactions
No Histopathological discrimination.
No CELL CULTURE discrimination
No ELECTROM MICROSCOPICAL discrimination
5
2
3
4
6
7
‫ال‬ ‫بسبب‬ ‫مهمة‬ ‫ليست‬ dna homology
In dermatopathology, the Tzanck test, also Tzanck smear,
is scraping of an ulcer base to look for Tzanck cells. It is
sometimes also called the chickenpox skin test and the
herpes skin test. Tzanck cells (acantholytic cells) are found
in: Herpes simplex. Varicella and herpes zoster.
Four herpesviruses: HSV types 1 and 2, VZV, and CMV induce
the formation of multinucleated giant cells, which can be seen
microscopically in the lesions.
The importance of giant cells is best illustrated by the Tzanck smear, which reveals
multinucleated giant cells in a smear taken from the painful vesicles . Arrow
points to a multinucleated giant cell with approximately eight nuclei
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
Oro-pharyngeal dis= ( HSV 1+2)
Primary infection {children }:
• Fever + sore throat
+ vesicular & ulcerative lesions(buccal/
gingival ).
Primary infection : (adults):
*Acute pharyngitis & Acute tonsillitis ..
Recurrent lesions :
* Border of lip
1
A: Primary herpes simplex gingivostomatitis B: Recurrent herpes simplex labialis
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
Kerato- conjunctivitis blindness
• HSV 1
1- Corneal ulcers .
2- Vesicles lesions on Eye Lids .
Genital Herpes : HSV2 usually :
* Vesicular & Ulcerative lesions {
penis , cervix , vulva, vagina ,
perineum ) .
2
3
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
Cutaneous Herpes
infection :
A.{ Burns = Fatal }
+
B.{ Eczema = Fatal }.
C. General skin infections
(primary + recurrent)
4
Eczema Herpeticum
A rare but Severe Cutaneous Herpes infection at sites of skin
, long term usage
burns
,
atopic dermatitis
by=
damage produced
eczema
or
topical steroids
of
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf
D- Traumatic Herpetic
infection : ( Only in
abrasions ) 
Fingers of dentists & hospital personal 
Herpetic
Whitlow.
Herpetic
whitlow
Painful, coalescing
vesicles with
surrounding erythema on
fingers
history revealed that the patient regularly bit his nails.
Positive results on direct fluorescent antibody tests and
viral cultures from digital lesions confirmed type 1 HSV
infection
5
Encephalitis :
HSV 1
*Most common cause of sporadic fatal
encephalitis .
** Usually affecting one brain hemisphere in
relation to the side of the affected ganglion
with the latent HSV infection
Neonatal Herpes
Intra-uterine
During birth ( 75%)
After birth .
• Mortality 50%.
* Almost always= Symptomatic.
6
75% HSV 2 25% HSV 1
Neonatal Herpes
3
Categories
Localized lesion
( skin ,eye , mouth)
Encephalitis
+- skin infection
Disseminated disease
+ death
(=pneumonitis or DIC)
Severe infections in immunocompromized pts.
• HSV1+2
• Spread to respiratory esophageal 
intestinal tissue & other organs .
•Most cases=
Reactivated
Infections.
7
Lab. Diagnosis
1- Isolation & identification.
2-Typing of HSV-Antigens & Nucleic
acid by:
A - Monoclonal Abs B- Restriction
Enzymes analysis.
3- DNA detection (PCR and ISH)
4- Serology ( IgM IgG Specific for
HSV 1&2 )
Immunity HSV 1 & 2
• Passively from the mother to baby ( 1st 6 m).
• Primary infection ( 6m – 2 years )
• Anti HSV 1 Abs = child hood & until adolescents
• Anti HSV 2 Abs = during adolescence & sexual
activity
• Abs  Do not prevent re-infection
or reactivation ::::::: but modify infection .
• Cell Mediated Immunity  Control
infection, re-infection & reactivation
Geting IgG
Prevention of HSV-1 or HSV-2 :
2…Chemoprophylaxis: Valacyclovir and Famciclovir
A… Suppression of recurrent lesions+ frequency of
recurrences
B…. Reduces shedding of the virus + transmission
3… Operations:
- Cesarean section: For women, at term, have genital lesions or positive
viral cultures
- Circumcision: reduces the risk of infection by HSV-2
1…Avoiding contact:
with the vesicular lesion or ulcer
Still, No Approved Vaccines against
HSV-1 or HSV-2
Treatment of HSV-1 or HSV-2 ::
1. Acyclovir
2. Valacyclovir
3. Vidarabine
Effective against HSV
Inhibitors of l DNA synthesis.
 Suppress clinical manifestations
 Shorten healing time
 Reduce recurrences of genital herpes.
 No effects on latent HSV in sensory ganglia.
THE SUMMARY
1.. Some Herpes viruses have carcinogenic
potential in a range of human cancers.
2.. Herpes simplex 1&2 viruses associated
with a range of human diseases that are
difficult on clinical bases being clearly
attributed to a specific type of them.
3..A list of diagnostic facilities can
differentiate between these two Herpes
simplex types.
Thank you

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HERPES VIRUS 12 LGT-66_882a9fdb0d6913bb7e1a8c57fee8335b.pdf

  • 1. Herpes viruses =Herpesviridae PROFESSOR DR. SAAD HASAN MOHAMMED ALI Ph. D. VIROLOGY 2022
  • 3. OBJECTIVES 1.. To preview the virological properties and classification bases of the viral members of Herpesviridae. 2..To list the range of human diseases caused by the two types of Herpes simplex viruses. 3..To list the range of diagnostic methods to differentiate between these two Herpes viral types. 4..To outline the control measures against Herpes simplex viruses.
  • 6. Examples Subfamily Latent Infections Genus Official Name ("Human - Herpesvirus") Common Name Alpha Neurons Simplex 1 Herpes simplex virus type 1 2 Herpes simplex virus type 2 Varicello 3 Varicella- zoster virus Beta Glands, kidneys Cytomegalo 5 Cytomegalo virus Lymphoid tissue Roseolo 6 Human herpesvirus 6 7 Human herpesvirus 7 Gamma Lymphoid tissue Lymphocrypto 4 Epstein-Barr virus Rhadino 8 Kaposi sarcoma- associated herpesvirus HERPESVIRUSES
  • 7. HUMAN HRPESVIRUSES  (100 Animal species). ( 8 Humans species). Herpes Simplex Virus 1 and 2 (HHV1&2) Varicella-Zoster Virus (HHV3) Epstein-Barr Virus (HHV4) Cytomegalovirus ( HHV5) Human Herpesvirus 6 (HHV6) Human Herpesvirus 7 (HHV7)  Kaposi-Sarcoma Associated- Herpesvirus (KSHV) (HHV8)
  • 9. All= Morphologically Identical: Icosahedral Enveloped Double stranded DNA genome. DNA homology: 1-HSV 1 & 2 (50%) 2- HHV 6 & 7 (30-50%) • Viral-Specific Enzymes= DNA polymerase & Thymidine kinase
  • 11. All= Morphologically Identical Different herpes viruses cannot be distinguished by electron microscopy Herpes virus particles from human vesicle fluid (X 140,000). (JAWETZ 2019)
  • 12. All =Characteristic DISEASE: Primary Infection  Latent Infection  Reactivation ((( frequently, but not always, associated with Further disease))).
  • 13. Some HHVs= Associated with Tumors and Carcinomas HSV-2 Cervical Carcinoma CMV COLONIC CARCINOMA PROSTATIC CARCINOMA CERVICAL CARCINOMA EBV Burkitt's lymphoma Nasopharyngeal Carcinoma HHV-8 Kaposi sarcoma in HIV.
  • 14. Replication Cycle of Herpes Viruses in General 1- Attachment = Cellular Receptors = Heparan Sulphate 2- Fusion 3- Uncoating  Release of viral DNA 4- Transcription of Alpha genes  Alpha –proteins (Cellular Preparation) 5-Transcription Beta genes  Beta- proteins = (ENZYMES). 6- Viral DNA replication  Viral DNA . 7- Transcription Gamma genes  Gamma – proteins= = Structural Proteins= Empty Capsids Immediate early Early Late
  • 15. Replication cycle(Continued…) 8- Packaging= DNA into capsids . 10- Accumulation of viral glycoproteins on the nuclear membrane . 11- Get Envelope from nuclear membrane . 12- VIRUSES GO OUT THE CELL through {Endoplasmic Reticulum}
  • 18. Herpes simplex viruses Background: Ubiquitous, host-adapted pathogens that cause a wide variety of disease states.  Two types exist: Both are closely related but differ in epidemiology. The term herpes is derived from the Greek word “to creep or crawl” Dates back to early Greek civilization, approximately 2000 years ago, in reference to the spreading nature of herpetic skin lesions. ‫مكان‬ ‫كل‬ ‫في‬ ‫موجودة‬
  • 21. Latent infections for both herpes simplex and varicella-zoster viruses. Primary infections occur in childhood or adolescence, followed by establishment of latent virus in the cerebral or spinal ganglia. Later activation causes recurrent herpes simplex or zoster. Recurrences are rare for zoster. CMI=Cell-Mediated Immunity.
  • 22. METHODS TO DIFFERENTIATE BETWEEN THE TWO TYPES OF HERPES SIMPLEX VIRUSES
  • 23. CLINICAL BASES: According To Anatomical Land mark of Waist ??? LESIONS ABOVE WAIST=TYPE 1 LESIONS BELOW WAIST=TYPE 2 Waist HSV 1 HSV 2 1
  • 24. HSV-1 is traditionally associated with orofacial disease, whereas HSV-2 is traditionally associated with genital disease.  Lesion location, however, is not necessarily indicative of viral type, as HSV-1 is associated with genital infections more often than HSV-2 in some unique subpopulations.
  • 25. Egg inoculation= Pocks size. DNA Finger Printing= ‫فايروسات‬ ‫من‬ ‫نوع‬ ‫لكل‬ ‫النووي‬ ‫الحمض‬ ‫بصمة‬ • Different Bands Size of The Two Types of HSV- DNA = by doing Restriction Enzymes analysis. Different Serological Reactions No Histopathological discrimination. No CELL CULTURE discrimination No ELECTROM MICROSCOPICAL discrimination 5 2 3 4 6 7 ‫ال‬ ‫بسبب‬ ‫مهمة‬ ‫ليست‬ dna homology
  • 26. In dermatopathology, the Tzanck test, also Tzanck smear, is scraping of an ulcer base to look for Tzanck cells. It is sometimes also called the chickenpox skin test and the herpes skin test. Tzanck cells (acantholytic cells) are found in: Herpes simplex. Varicella and herpes zoster.
  • 27. Four herpesviruses: HSV types 1 and 2, VZV, and CMV induce the formation of multinucleated giant cells, which can be seen microscopically in the lesions.
  • 28. The importance of giant cells is best illustrated by the Tzanck smear, which reveals multinucleated giant cells in a smear taken from the painful vesicles . Arrow points to a multinucleated giant cell with approximately eight nuclei
  • 30. Oro-pharyngeal dis= ( HSV 1+2) Primary infection {children }: • Fever + sore throat + vesicular & ulcerative lesions(buccal/ gingival ). Primary infection : (adults): *Acute pharyngitis & Acute tonsillitis .. Recurrent lesions : * Border of lip 1
  • 31. A: Primary herpes simplex gingivostomatitis B: Recurrent herpes simplex labialis
  • 33. Kerato- conjunctivitis blindness • HSV 1 1- Corneal ulcers . 2- Vesicles lesions on Eye Lids . Genital Herpes : HSV2 usually : * Vesicular & Ulcerative lesions { penis , cervix , vulva, vagina , perineum ) . 2 3
  • 35. Cutaneous Herpes infection : A.{ Burns = Fatal } + B.{ Eczema = Fatal }. C. General skin infections (primary + recurrent) 4
  • 36. Eczema Herpeticum A rare but Severe Cutaneous Herpes infection at sites of skin , long term usage burns , atopic dermatitis by= damage produced eczema or topical steroids of
  • 39. D- Traumatic Herpetic infection : ( Only in abrasions )  Fingers of dentists & hospital personal  Herpetic Whitlow.
  • 40. Herpetic whitlow Painful, coalescing vesicles with surrounding erythema on fingers history revealed that the patient regularly bit his nails. Positive results on direct fluorescent antibody tests and viral cultures from digital lesions confirmed type 1 HSV infection
  • 41. 5 Encephalitis : HSV 1 *Most common cause of sporadic fatal encephalitis . ** Usually affecting one brain hemisphere in relation to the side of the affected ganglion with the latent HSV infection
  • 42. Neonatal Herpes Intra-uterine During birth ( 75%) After birth . • Mortality 50%. * Almost always= Symptomatic. 6 75% HSV 2 25% HSV 1
  • 43. Neonatal Herpes 3 Categories Localized lesion ( skin ,eye , mouth) Encephalitis +- skin infection Disseminated disease + death (=pneumonitis or DIC)
  • 44. Severe infections in immunocompromized pts. • HSV1+2 • Spread to respiratory esophageal intestinal tissue & other organs . •Most cases= Reactivated Infections. 7
  • 45. Lab. Diagnosis 1- Isolation & identification. 2-Typing of HSV-Antigens & Nucleic acid by: A - Monoclonal Abs B- Restriction Enzymes analysis. 3- DNA detection (PCR and ISH) 4- Serology ( IgM IgG Specific for HSV 1&2 )
  • 46. Immunity HSV 1 & 2 • Passively from the mother to baby ( 1st 6 m). • Primary infection ( 6m – 2 years ) • Anti HSV 1 Abs = child hood & until adolescents • Anti HSV 2 Abs = during adolescence & sexual activity • Abs  Do not prevent re-infection or reactivation ::::::: but modify infection . • Cell Mediated Immunity  Control infection, re-infection & reactivation Geting IgG
  • 47. Prevention of HSV-1 or HSV-2 : 2…Chemoprophylaxis: Valacyclovir and Famciclovir A… Suppression of recurrent lesions+ frequency of recurrences B…. Reduces shedding of the virus + transmission 3… Operations: - Cesarean section: For women, at term, have genital lesions or positive viral cultures - Circumcision: reduces the risk of infection by HSV-2 1…Avoiding contact: with the vesicular lesion or ulcer Still, No Approved Vaccines against HSV-1 or HSV-2
  • 48. Treatment of HSV-1 or HSV-2 :: 1. Acyclovir 2. Valacyclovir 3. Vidarabine Effective against HSV Inhibitors of l DNA synthesis.  Suppress clinical manifestations  Shorten healing time  Reduce recurrences of genital herpes.  No effects on latent HSV in sensory ganglia.
  • 49. THE SUMMARY 1.. Some Herpes viruses have carcinogenic potential in a range of human cancers. 2.. Herpes simplex 1&2 viruses associated with a range of human diseases that are difficult on clinical bases being clearly attributed to a specific type of them. 3..A list of diagnostic facilities can differentiate between these two Herpes simplex types.