Eka Noneng Nawangsih, dr.

, MKes

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There are many viral skin infections.

They range from the common to the

rare, from the mild to the severe

Causing just skin infection to those with

associated systemic disease.
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 Viruses are obligate intracellular parasites

The principle site of attack in the skin is the

epidermis .

These may cause localized or systemic mani-

festations that varies from erythematous
lesions, vesiculation, ulceration , scarring or
severe constitutional symptoms .
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 Herpes- Varicella
Herpes
viridae : Zoster

Moluscum
Poxviridae Smallpox
contagiosum

Papilloma- Wart
(Verruca
viridae vulgaris)
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Subfamily Virus Abbreviation
Alphaherpesvirinae
Human herpes virus 1 Herpes simplex type 1 HSV-1
Human herpes virus 2 Herpes simplex type 2 HSV-2
Human herpes virus 3 Varicella-zoster virus VZV

Gammaherpesvirinae
Human herpes virus 4 Epstein-Barr virus EBV
Human herpes virus 8 Kaposis sarcoma HHV-8
related virus
Betaherpesvirinae
Human herpes virus 5 Cytomegalovirus CMV
Human herpes virus 6 Herpes lymphotropic virus HHV-6
Human herpes virus 7 Human herpes virus 7 HHV-7
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VIRUS MEANS OF PORTAL OF ENTRY INITIAL
TRANSMITION TARGET CELLS
HSV-1 Direct contact Mucous membrane, skin Ephitelial

HSV-2 Direct contact Mucous membrane, skin Ephitelial

VZV Inhalation, Direct Respiratory tract, Mucous Epithelial
contact membrane ?
CMV Saliva, Blood, Urine Blood stream, Mucous Nuetrophils,
(?), Semen membrane Monocyte, Others
EBF Saliva, Blood Mucous membane, Blood B lymphocyte
streams
HHV-6 Respiratory tract, ? T lymphocyte
Close contac (?)
HHV-7 ? ? T lymphocyte
HHV-8 Saliva ? ? 7
 STRUCTURE OF HERPESVIRUSES

Unique features of Herpesviruses :

Are large, enveloped, contain double-stranded

DNA genome
150 200 nm
DNA core is surrounded by an icosahedral
capsid containing 162 capsomeres. This enclosed
by a glycoprotein containing envelope
Herpesviruses encode several glycoproteins for
viral attachment, fusion, and immune escape
 DNA replication and
Herpes viruses encoded
assembly occur in
many proteins that nucleus, virus buds
regulate m-RNA & DNA from nuclear
synthesis membrane and
Encoded enzyme DNA released by exocytosis
polymerase that and cell lysis
promote viral DNA
replication and that are
good targets for
antiviral drugs
HERPES SIMPLEX VIRUS
Extremely widespread in the human population
Exhibit a broad host range, being able to replicate
in many types of cells
Grow rapidly and are highly cytolytic
Responsible for a spectrum of diseases
gingivostomatitis
keratoconjunctivitis
encephalits
genital herpes
infections of newborn
Are frequently latent in neuron
Properties of viruses :

Two distinct herpes simplex viruses :

type 1 & type 2
Their genomes are similar in organization &
exhibit substantial approximately
50% DNA sequence of homology
Can be distinguished by restriction enzyme
analysis of viral DNA
Cross-react serologically, caused by
produce common antigens (7 12 Ags), but
some unique proteins exist for each
type (type specific antigens)
The two viruses differ in :
their mode of transmission
HSV-1 is spread by contact,
usually involving infected saliva
HSV-2 transmitted sexually or
from maternal genital infection
to a newborn
PRIMARY INFECTION
mucous membrane, skin AXON
(eyes, mouth, throat)

Multiplication

Regional lymphnode

Multiplication

Blood (Viremia) GANGLION

Organs
Ab & Cellular immunity
PRIMARY INFECTION LATENT INFECTION
Oropharyngeal HSV-1 Virus resides in latently
infections results in infected ganglia in a
latent infection in the nonreplicating state, only
trigeminal ganglia a very few viral genes are
expressed
Genital HSV-2 infection
lead to latently infected Viral persistence in latently
sacral ganglia infected ganglia lasts for
the lifetime
Primary infections :
usually mild, in fact More than 80% of the
most are asymptomatic human population harbor
(85 90%) HSV-1 in latent form, only
a small portion
recurrence
 Vesicular eruption at the skin or mucous
membrane
Incubation period is short :
3 5 days, with a range of 2 12 days
Clinical manifestation 2 categories
Primary infection
Reactivation

HSV-1 : oropharyngeal area

HSV-2 genital
Pr

Primary infection
Gingivostomatitis + -
Pharyngotonsilitis + -
Keratoconjunctivitis + -
Neonatal infections +
Recurrent infection
Cold sores, fever blisters + -
Keratitis + -
Primary or recurrent infection
Cutaneous herpes
Skin above the waist + -
Skin below the waist - +
Hands or arms + +
Herpetic whitlow + +
Eczema herpeticum + -
Genital herpes +
Herpes encephalitis + -
Herpes meningitis + +
1. Oropharyngeal disease : cluster of vesicles,
most commonly localized at the border of
the lip, painful, 4 5 days
2. Keratoconjunctivitis : common & appear as
dendritic keratitis or corneal ulcers or
vesicles on the eyelids
3. Genital herpes : common & tend to be
mild, a limited number of vesicles, heal in 10
days
Provocation :
Common cold
UV
Underlying disease
Stress
Hormonal (menstrual cycle)
HSV-2 : Oncogenic virus Ca-cervix & vulva
transformation of cell culture
inoculation of animal tumor
 Many newborns acquire passively
transferred maternal Abs, lost during 6
months, not totally protected against
infection of newborns
During primary infections, IgM Abs appear
transiently, and followed by IgG & IgA that
persist for long period
Abs do not prevent reinfection or
reactivation of latent virus, but maybe
subsequent disease
 ISOLATION & IDENTIFICATION
Specimens : swab or vesicle fluid
HSV has a wide host range
many cell culture system are susceptible
Appearance of CPE in cell cultures in 2 3 days
identified by Nt test or immunofluorescence
staining
Hybridization using DNA probes & DNA
amplification
SEROLOGY
Abs appear in 4 7 days after infection, reach a peak
after 2 4 weeks
can be measured by Nt, CF, ELISA, RIA, IF
 Inhibitors of viral DNA synthesis
The drugs inhibits virus replication & suppress
clinical manifestation
HSV remain latent in sensory ganglia
Acyclovir (acycloguanosine) : topical,
intravenous, oral
Vidarabine : more toxic
VARICELLA-ZOSTER VIRUS (VZV)

Varicella (chickenpox) :
a mild, highly contagious disease
chiefly in children
characterized clinically by a
generalized vesicular eruption of the
skin & mucous membranes
The disease may be severe in adults &
immunocompromised children
Zoster (shingles) :
a sporadic, incapacitating disease of
adults or immunocompromised
individuals
characterized by rash limited to distribution
to the skin innervated by a single sensory
ganglion
lesions similar to those of varicella
PROPERTIES OF VIRUSES

VZV is morphologically identical to HSV

The virus propagated in cultures of
human embryonic tissue, produce
typical intranuclear inclusion bodies
Cytopathic changes are more focal and
spread much more slowly than HSV
PATHOGENESIS

Varicella : route of infection is the

mucosa of the upper respiratory tract or
conjunctiva

blood multiple cycle of replication

skin
Zoster :
skin lesion histopathologicaly identical to
varicella
acute inflammation of the sensory nerve &
ganglia
often only a single ganglion may be
involved
as a rule the distribution of lesions in the
skin corresponds closely to the areas of
innervation from an individual dorsal root
ganglion
Varicella Herpes Zoster
 Previous infection with varicella is believe to
confer lifelong immunity to varicella
However, zoster can occur in the presence of
relatively high level of Nt Ab to varicella
Laboratory diagnosis
Stained smear of scraping or swabs of
the base vesicles :
multinucleated giant cells
Virus isolated from vesicle fluid using
culture of human cells 3 7 days
Cytopathic effects develop more slowly
Gamma globulin of high VZV Ab
titer (VZ Ig) can be used to
prevent the development of the
illness of immunocompromised
patients exposed to varicella
It has no therapeutic value once
varicella has started
Antiviral : acyclovir, valacyclovir,
vidarabine
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The largest & most complex of viruses known
Smallpox first appeared in China and the Far East at
least 2000 years ago.
The family encompasses a large group of agents,
morphologically similar,
share a common nucleoprotein
antigen
The group includes variola virus
etiologic agent of smallpox,
disease has most affected humans
throughout the world
recorded history until elimination in 1977
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Eradication & vaccination all over the world started
by WHO (1967)

Smallpox has been declared eradicated from the

world (May 1980) after an extensive campaign
coordinated by WHO

Vaccinia virus is under intensive study as a vector

for introducing active immunizing genes as live-
virus vaccines for a variety of viral diseases of
humans & domestic animals
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 GENUS VIRUS PRIMARY DISEASES
HOST
Orthopoxvirus Variola Humans Small pox (now extinct)
Vaccinia Humans Localized lesion, used for smallpox
vaccination
Buffalopox Water Buffalo Human infection rare, local
Monkeypox Monkeys Human infection rare, general
Cowpox Cows Human infection rare, local
Parapoxvirus Orf Sheep Human infection rare, local
Pseudocowpox Cows Milker nodes
Bovine Popular Cows
Stomatitis
Molluscipox- Moluscum Humans Many benign skin nodule
virus contagiosum
Yatapoxvirus Tanapox Monkeys Human infection rare, local
Yabapox Monkeys Human infection rare, local,
accidental , localized skin tumor 37
 Virion : complex structure,
oval or brick shape particle,
measuring 400 X 230 nm,
external surface shows ridges,
contain core & lateral bodies
Composition : DNA (3%), protein (90%),
lipid (5%)
Genome : ds-DNA, linear, size 130 375 kbp,
low G + C content (30 40%),
except Parapoxvirus (63%)
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 Proteins : - contain more than 10 polypeptides,
- many enzymes in core including
DNA-dependent RNA polymerase,
- including transcriptional system
Envelope : a lipoprotein membrane

Replication : cytoplasmic

Outstanding characteristics :
- very resistant to inactivation
- virus encoded protein help evade
host immune defense system
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 Multiplication cycle takes place in the cytoplasm,
in which they form inclusion bodies
Nuclear factors involved in transcription and
virion assembly
Propagation in the laboratory : most poxviruses
can be propagated on the chorioallantoic
membrane of the 10 12 days old chick embryo,
form circumscribed pocks, 2 - 3 mm or in cell
cultures
Molluscum contagiosum virus has not so far been
grown in the laboratory

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 Virus attaches to glycosaminoglycans (GAGs) on the
surface of the target cell or by components of the
extracellular matrix, triggering membrane fusion and
release of the virus core into the cytoplasm.

Early phase: early genes are transcribed in the cytoplasm

by viral RNA polymerase. Early expression begins at 30
minutes post-infection.

Core is completely uncoated as early expression ends, viral

genome is now free in the cytoplasm.
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 Intermediate phase: Intermediate genes are
expressed, triggering genomic DNA
replication at approximately 100 minutes
post-infection.

Late phase: Late genes are expressed from

140 min to 48 hours post-infection, producing
all structural proteins.

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 Assembly of progeny virions starts probably in
association with internal membranes of the
infected cell, producing an spherical immature
particle. This virus particle matures into brick-
shaped intracellular mature virion (IMV).

IMV virion can be released upon cell lysis, or can

acquire a second double membrane from trans-
Golgi and bud as external enveloped virion (EEV)
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Control & eradication of smallpox :
Edward Jenner (1798) introduced
vaccination with live cowpox virus
In 1967 WHO introduced a worldwide
campaign to eradicate smallpox
The last Asiatic case occurred in Bangladesh
(1975)
The last natural victim was diagnosed in
Somalia (1977)
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 The vaccine was easily
prepared, stable, safe and
effective
It could be given simply by
personnel in the field
Humans are the only natural
host
Only I type of smallpox virus

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Vaccinia virus : Variola virus :
Used for smallpox vaccine

Has a broad host range Has narow host range

Nucleotide sequences Nucleotide sequences
192 kb 186 kb

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Portal of entry : mucous membranes of
respiratory tract

1. Primary multiplication in lymphoid tissue

draining the site of entry
2. Transient viremia & infection of RE cells
throughout the body
3. Secondary phase of multiplication
4. Secondary & more intense viremia
5. Clinical disease
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Smallpox was transmitted by respiratory route from
lesions in the respiratory tract of patients in the early
stage of the disease.

During the 12 day incubation period, the virus was

distributed initially to the internal organs and then to
the skin.

Variola major caused severe infections with 20-50%

mortality, variola minor with <1% mortality.
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Management of outbreaks depended on
the isolation of infected individuals and the
vaccination of close contacts.

The vaccine was highly effective. If given

during the incubation period, it either
prevented or reduced the severity of clinical
symptoms.

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At least 9 different poxviruses
cause disease in humans, but
variola virus (VV) and vaccinia are
the best known. VV strains are
divided into variola major (25-
30% fatalities) and variola minor
(same symptoms but less than
1% death rate).
"Variolation" = the administration
of material from known smallpox
cases (hopefully variola minor!!!)
to protect recipients - practiced
for at least 1000 years (Chinese)
but risky - Jenner was nearly
killed by variolation in 1756!
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An attack of smallpox complete protection
against re-infection
Vaccination with vaccinia induced immunity
against variola virus at least 5 years &
sometimes longer
Neonates of vaccinated, immune mother
receive maternal antibody transplacentally,
persists for several months.
After that time, artificial immunity can be
produced by vaccination
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Molluscum contagiosum is a specifically human
disease of worldwide distribution.

The incubation period varies from 1 week to 6

months.

The lesion begins as a small papule and gradually

grows into a discrete, waxy, smooth, dome-
shaped, pearly or flesh-coloured nodule.

Usually 1-20 lesions but occasionally they may be

present in hundreds.
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In children, the lesions are found on the
trunk and the proximal extremities.

In adults they tend to occur on the trunk,

pubic area and thighs.

Individual lesions persist for about months,

but the disease usually lasts 6 to 9 months.
Constitutional disturbance is rare.

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The disease occurs world-wide and is spread by direct
contact or fomites. In general it tends to occur in
children. The disease by may transmitted from skin
to skin after sexual intercourse.

A diagnosis can usually be made on clinical appearance

alone.

Unlike other poxviruses, molluscum have not been

demonstrated to grow in cell culture.

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Infection is usually benign and painless,
with spontaneous recovery in most cases.

Where treatment is required for cosmetic

reasons, curretage, cryotherapy with
liquid nitrogen, silver nitrate etc. which are
routinely used for the removal of warts.

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Molluscum contagiosum is a superficial skin
infection.
The virus invades the skin causing the
appearance of firm, flesh-colored,
doughnut-shaped bumps, about 2-5 mm in
diameter.
Their sunken centers contain a white,
curdy-type material. The bumps can occur
almost anywhere on the body including the
buttocks
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Close physical contact is usually necessary for
transmission; indirect transmission from shared
towels, swimming pools, etc., may also be
responsible for infection.

The incubation period varies from several weeks to

several months. Shaving or scratching may cause
the infection to spread.

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 COMPLICATIONS

If scratched, the bumps can become infected with

bacteria.

DIAGNOSIS

The diagnosis is based on the typical appearance of

the bumps.
No diagnostic test for this virus is available.

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Avoid shaving infected areas.

Treatment is done for aesthetic reasons and to prevent

spread of the virus.

The goal of treatment is to remove the soft center, after

which the bump goes away.

Your health care provider may use a curette (sharp,

spoon-shaped instrument) to remove the centers.

Freezing the lesion with liquid nitrogen or nitrous oxide is

an alternative treatment.
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RISKS OF TREATMENT

There is a slight risk of minimal scarring.

Observe for signs of infection that include

redness, swelling, pus-like drainage, or
increased soreness at the site.

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 More than 70 genotypes HPV have been identified in
human specimens.

Predilection for infection at the junction of

squamous and columnar ephitelium.

HPV types 6 and 11 benigh genital warts in male

and female rarely become malignant
Types 16, 18, 31, and 45 warts lesions of vulva,
cervix and penis. Types 16 progress malignancy
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 Familia : Papovaviridae
Genus : Papillomavirus
Spesies : Human Papillomavirus

Caracteristic Virus :
Non-enveloped.
Small, icosahedral, about 52-55 nm in size.
Genom : circular ds DNA about 8 kb in size,
associated with cellular histones
Have not been grown in vitro
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 Only one strand of the genome is transcribed and yield
two classes of proteins:
a) Early Proteins: non-structural regulatory proteins
(E1-E7).
b) Late Proteins: the structural proteins L1 and L2

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 A single molecule of circular dsDNA is
contained within the capsid, which is
composed of 72 capsomers (60 hexameric +
12 pentameric).

There are 2 capsid proteins, 1 major (L1) and 1

minor (L2).

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 Sexual contact. This is the most common way
amongst adults.
Oral sex. HPV appears to prefer the genital area
to the mouth however.
Vertical (mother to baby) transmission.
Auto (self) inoculation from one site to another.
Fomites (i.e. from objects like bath towels). It
remains very controversial whether warts can
spread this way

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