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Saleh Bahaj
Prof. of Medical
Microbiology/Immunology
Herpesviridae
Lecture 4
Objectives
By the end of this lecture the students will be able to:-
I) Definition
II) Pathogenesis
III) Diseases
IV) Lab. Diagnosis
V) Treatment
VI) Prevention
 Herpes simplex virus-1
 Herpes simplex virus-2
Objectives
 Introduction
DNA
Enveloped Non-enveloped
dsDNA
Herpesviridae
Hepdnavridae
(HBV)
Poxviridae
dsDNA
ssDNA
•Adenoviridae
•Papovaviridae
Parvoviridae
* Parvovirus B19
HHAPPPy
DNA
All DNA viruses
dsDNA EXCEPT
Parvovirus B19
(ssDNA)
DNA
All DNA viruses
Linear EXCEPT
Papovavirus
(circular)
DNA
All DNA viruses
Icosahedral
EXCEPT
Poxviruses
(Complex)
DNA
All DNA viruses
Replicate in nucleus
(inclusion bodies present
intranuclear ) EXCEPT
Poxvirus in cytoplasm
(intracytoplasmic)
Herpes Family
1) Herpes simplex
Viruses HSV(1&2)
2) Varicella-Zoster
virus (VZV)
3) Cytomegalovirus
(CMV)
4) Epstein-Barr
virus (EBV)
5)Human herpes
virus HHV(6&7)
7)Human herpes
virus (HHV8)
Herpes Family
Herpein = Creep
Herpesviridae
Characteristic
Characteristic of Herpesviridae
All members are
dsDNA with
enveloped
dsDNA
1
Characteristic of Herpesviridae
Enveloped
Icosahedral
2
Characteristic of Herpesviridae
HSV-1 HSV-2 VSV EBV
CMV HHV-6 HHV-7 HHV-8
3 Similar morphology
Characteristic of Herpesviridae
4 Latency
Characteristic of Herpesviridae
5
linked with
tumor
Characteristic of Herpesviridae
6
Response
to anti-viral drugs
Characteristic of Herpesviridae
Similar
morphology
2
3
4
5
1) Herpes simplex
virus type-1 (HSV-1)
Herpesviridae
I) Definition of (HSV-1)
HSV-1
HSV-2
Belt
Herpes labialis
II) Pathogenesis oh HSV-1
Herpes labialis
Keratoconjunctivitis
III) Diseases
Gingivostomatitis
Herpetic whitlow
Herpetic whitlow
III) Diseases
Encephalitis
III) Diseases
Aseptic
Meningitis
III) Diseases
Herpes labialis Herpetic whitlow
Gingivostomatitis Keratoconjunctivitis
Encephalitis Aseptic meningitis
1) Herpes simplex
virus type-1 (HSV-1)
IV) Lab. diagnosis
IV) Lab. diagnosis
Clinically
IV) Lab. diagnosis
Specimen
 Vesicular fluid
 Scraping of ulcer
 Corneal scrapping
 CSF
1) Direct virus demonstration
A- Tzanck smear
(multinucleated
giant cells)
Giemsa stain
(Light Microscopy) Intranuclear
inclusion bodies
 Scraping of ulcer
1) Direct virus demonstration
C) Detection of
viral antigen by
DIF
From specimen
Anti-
HSV-1
1) Direct virus demonstration
D) Detection of
Nucleic acid by
PCR
2) Viral Isolation
A) Isolation the
virus in tissue
culture (monkey
kidney) by
Immunofluoresence
2) Viral Isolation
A) Isolation the
virus in tissue
culture (monkey
kidney) by
Immunofluoresence CPE
3) Serological tests
A) Detection of
IgM/IgG
ELISA
Serum
 Encephalitis
1) Herpes simplex
virus type-1 (HSV-1)
V) Treatment
V) Treatment
Acyclovir
nucleoside-mimic
V) Treatment
Acyclovir
(Prevent replication)
Effect on viral
DNA polymerase enzyme
1) Herpes simplex
virus type-1 (HSV-1)
VI) Prevention
VI) Prevention
Avoid contact
With herpetic
lesion
VI) Prevention
Avoid
Kissing
VI) Prevention
Hand
washing
Q1
Herpesviridea family is characterized by
Monocyte
2-3 days
Latency
Reactivation
Chronic infection
Response to viral therapy
Q2
Monocyte
2-3 days
HSV-1 cause the following diseases
Monocyte
2-3 days
Gingivostomatitis
Herpes labialis
Herpetic whitlow
Neonatal herpes
Q3
Monocyte
2-3 days
HSV-1 remain latent
Monocyte
2-3 days
Monocyte
2-3 days
Sacral ganglia
Trigeminal ganglia
Lymphoid cells
B cells
Q4
Monocyte
2-3 days
During latency, Herpes simplex virus-1 causes
Genital herpes
Herpetic whitlow
Keratoconjunctivitis
No clinical manifestations
2) Herpes simplex
virus type-2 (HSV-2)
I) Definition
II) Pathogenesis
III) Diseases
IV) Lab. Diagnosis
V) Treatment
VI) Prevention
I) Definition of HSV-2
 ds DNA
 enveloped
 icosahedral virus
 attacks the
mucous membranes
of the genital tract.
2) Herpes simplex
virus type-2 (HSV-2)
II) Pathogenesis
II) Pathogenesis of HSV-2
Sexual
transmission
H H O
II) Pathogenesis of HSV-2
From mouth
to genital HSV-1
II) Pathogenesis of HSV-2
Vertical
transmission
II) Pathogenesis of HSV-2
Asymptomatic
Shedding
II) Pathogenesis of HSV-2
Sexual
transmission
Multiple
at site of entry
Formation of
vesicles
(ulcerate)
Sacral ganglia
2) Herpes simplex
virus type-2 (HSV-2)
III) Diseases
III) Diseases
1- Genital
herpes
Vesicular Lesions
On glans (end of
the penis), shaft of
the penis.
III) Diseases
1- Genital
herpes
Maybe
Asymptomatic
III) Diseases
2- Neonatal
herpes
 Asymptomatic
 Generalized
disease
 Encephalitis
III) Diseases
2- Neonatal
herpes
Birth canal
III) Diseases
3- Cervical
cancer
Herpes simplex virus
type-2 (HSV-2)
IV) Lab. diagnosis
IV) Lab. diagnosis
Discus with your
team
How can you
diagnosis of HSV-2?
IV) Lab. diagnosis
Clinically
IV) Lab. diagnosis
Specimen
Vesicular fluid
Scraping of ulcer
IV) Lab. diagnosis
A- Tzanck smear
(multinucleated
giant cells)
Giemsa stain
(Light Microscopy)
Intranuclear
inclusion bodies
IV) Lab. diagnosis
B) Detection of
viral antigen by
DIF
From specimen
Anti-
HSV-2
IV) Lab. diagnosis
C) Detection of
Nucleic acid by
PCR
IV) Lab. diagnosis
D) Isolation the
virus in tissue
culture (monkey
kidney) by
Immunofluoresence
IV) Lab. diagnosis
D) Isolation the
virus in tissue
culture (monkey
kidney) by
Immunofluoresence CPE
Herpes simplex virus
type-2 (HSV-2)
V) Treatment
V) Treatment
Acyclovir
nucleoside-mimic
V) Treatment
 Acyclovir
(Prevent replication)
Effect on viral
DNA polymerase enzyme
2) Herpes simplex
virus type-2 (HSV-2)
VI) Prevention
Exercise-2
Compare between
HSV1 &HSV-2
Exercise-1
HSV-2
HSV-1
Item
2- Mode of
transmission
1- Target
3- Diseases
Lips, nose &
eyes
Genital
tract
Contact
Sexual
transmission
Herpes labials
Herpetic whitlow
Gingivostomatitis
Keratoconjunctivitis
Genital herps
Neonatal herpes
Exercise-1
HSV-2
HSV-1
Item
5- Specimen
for diagnosis
4- Latency Trigeminal
ganglia
Sacral
ganglia
Skin lesion
V) Test yourself
Q1
Monocyte
2-3 days
HSV-2 cause the following diseases
Monocyte
2-3 days
Genital herpes
Herpes labialis
Herpetic whitlow
Neonatal herpes
Q2
Monocyte
2-3 days
HSV-2 remain latent
Monocyte
2-3 days
Monocyte
2-3 days
Sacral ganglia
Trigeminal ganglia
Lymphoid cells
B cells
Q3
Monocyte
2-3 days
Infection with HSV-2 occurs by the
following modes
Sexual contact
Transplacental
Through birth canal
Reactivation of latent virus
Q4
Monocyte
2-3 days
During latency, Herpes simplex virus-2 causes
Genital herpes
Herpetic whitlow
Keratoconjunctivitis
No clinical manifestations
3) Varicella-Zoster
virus
I) Definition
II) Pathogenesis
III) Diseases
IV) Lab. Diagnosis
V) Treatment
VI) Prevention
I) Def. of Varicella-Zoster virus
 ds DNA,
 enveloped,
 icosahedral virus
leading
to generalized rash
3) Varicella-Zoster
virus
II) Pathogenesis
II) Pathogenesis of Varicella-Zoster virus
Varicella
(Chicken pox)
Zoster
(Shingles)
Primary
infection
Reactivation
infection
II) Pathogenesis of Varicella-Zoster virus
Droplets
Direct contact
with vesicle
Trancplacental
II) Pathogenesis of Varicella-Zoster virus
Respiratory
mucosa
II) Pathogenesis of Varicella-Zoster virus
Replication in
regional nodes
II) Pathogenesis of Varicella-Zoster virus
Blood
(1st viremia)
II) Pathogenesis of Varicella-Zoster virus
Into liver &
spleen
II) Pathogenesis of Varicella-Zoster virus
Blood
(2nd Vireamia)
II) Pathogenesis of Varicella-Zoster virus
Into
respiratory
mucosa
Into
mononuclear
cells
II) Pathogenesis of Varicella-Zoster virus
Transport to
skin &
mucous
membrane
II) Pathogenesis of Varicella-Zoster virus
Replication in
epidermal
cells
II) Pathogenesis of Varicella-Zoster virus
Skin rash
Virus in
dorsal root ganglia
Lesion
Umbilicate
Polymorphic
(macule, papule,
pustule , ulceration
 Centripetal rash (in smallpox
centrifugal ‫واليدين‬ ‫الرجلين‬ ‫األطراف‬ ‫في‬
distribution)
• Superficial Do not reach basal cell
layer (Healing without
disfigurement)
• Umbilicated lesion
• Polymorphic (papule, pustules,
vesicle at the same time in a same
II) Pathogenesis of Varicella-Zoster virus
Skin rash
Trunk
Face
limbs
II) Pathogenesis of Varicella-Zoster virus
The rash start
as macular
II) Pathogenesis of Varicella-Zoster virus
Rapidly evolves
papule
II) Pathogenesis of Varicella-Zoster virus
vesicle
(dew drops)
II) Pathogenesis of Varicella-Zoster virus
Pustule
& Crust
II) Pathogenesis of Varicella-Zoster virus
All stages may be
seen at one time
II) Pathogenesis of Varicella-Zoster virus
Droplets
Or contact
Respiratory
mucosa
regional
nodes
2nd
viremia
Into liver &
spleen
1ry viremia
Into
Mononuclear
cells
I.P 10-21 days
II) Pathogenesis of Varicella-Zoster virus
Into
mononuclear
cells
Transport to skin &
mucous membrane
dorsal root
ganglia
Skin rash
Replication in
epidermal cells
I.P 10-21 days
II) Pathogenesis of Varicella-Zoster virus
Pre-eruptive
stage
Fever (firstly)
Eruptive
stage
After 1-2
days
Malaise &
headache
Macule, papule, vesicle
& Pustule (Crusts)
Trunk Face Limbs
3) Varicella-Zoster
virus
II) Pathogenesis
Congenital
varicella syndrome
Congenital varicella syndrome
1st & 2nd trimester
the fetus is at increased
risk of developing
congenital varicella
syndrome
Congenital varicella syndrome
RARE
Mental retardation
Limb abnormalities
Eye abnormalities
3) Varicella-Zoster
virus
II) Pathogenesis
Zoster
Zoster
Varicella
(chickenpox)
Zoster(Shingles)
(Herpes Zoster)
Zoster
Zoster
Zoster = girdle
Singles
Zoster
Singles = inflammation
often
extends around
the middle of the body
Zoster
Reactivation of the virus
Zoster
A belt roses
from hell
Zoster
reactivation
of latent
varicella infection
3) Varicella-Zoster
virus
II) Pathogenesis
Zoster
Complication
1- postherpetic neuralgia
Constant pain at
the site (Stabbing
pain) for 1 month
or year in 50%
patients after the
rash heal.
2- Ophthalmic zoster
3) Varicella-Zoster
virus
III) Lab. diagnosis
III) Lab. diagnosis
Specimen
III) Lab. diagnosis
1) Direct A)Virus demonstration
B) Virus Isolation
2) Indirect
A)Serological tests
(Serum)
1) Direct virus demonstration
A- Tzanck smear
(multinucleated
giant cells)
Giemsa stain
(Light Microscopy)
1) Direct virus demonstration
Intranuclear
inclusion bodies
(Light Microscopy)
1) Direct virus demonstration
B) Detection virus
particles by
EM!!!!!
1) Direct virus demonstration
C) Detection of
viral antigen by
DIF
From specimen
1) Direct virus demonstration
D) Detection of
Nucleic acid by
PCR
2) Viral Isolation
A- Isolation the
virus in tissue
culture (monkey
kidney) by
Immunofluoresence
2) Viral Isolation
A- Isolation the
virus in tissue
culture (monkey
kidney) by
Immunofluoresence CPE
3) Serological tests
A) Detection of
IgM
Serum
 Recent Infection
3) Serological tests
A) Detection of
Antibodies
ELISA!!!!
Serum
3) Serological tests
4- Detection of rising titre of
IgG by ELISA
1/80
2nd sample after
7 days
1/320
Serum
Exercise 2
Discuss with
your team
What is the clinical
spot diagnosis of
Varicella (Chickenpox)
Answer of Exercise 2
Fever
Rash
(Starting in trunk)
Then
 Macule
 Papule
 Vesicle
 Pustule
Present at the
same time
1
2
3
3) Varicella-Zoster
virus
IV) Treatment
IV) Treatment
 Acyclovir
 Valacyclovir
 Both varicella or zoster
(Prevent replication)
IV) Treatment
 Avoid Aspirin
Reye’s syndrome
3) Varicella-Zoster
virus
V) Prevention
V) Prevention
Varivax (1995)
Zostavax (2006)
Shingrix (2017)
Chickenpox
Zoster
V) Prevention
A living attenuated
varicella vaccine
1995
(Varivax)
2 doses
V) Prevention
Zostavax
 Attenuated
 Single dose
 Older age (60y.)
V) Prevention
Zostavax
 Not used for
children
 Not substitute
for Varivax
(2017)
Recombinant
V) Prevention
V) Prevention
VZIG
V) Test yourself
Q1
Monocyte
2-3 days
The spot diagnosis of varicella
(Chickenpox)
Centripetal rash
All types of rash are present
Umbilicated lesion
Heal with scar
Q2
The mode transmission of Zoster
Droplets
Contact
Endogenous
Q3
Monocyte
2-3 days
The mode of transmission of varicella
(chickenpox)
Droplets
Contact
Endogenous
Q4
Monocyte
2-3 days
The varicella –zoster virus latent on
Trigeminal ganglia
Sacral Ganglia
B cells
No clinical manifestations
II) Pathogenesis of HSV-2
Multiple at site
of entry
(mucous membrane)
II) Pathogenesis of HSV-2
Formation of
vesicles
(ulcerate)
II) Pathogenesis of HSV-2
Sacral ganglia
Reactivation
(recurrent lesion)

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