Transcript Herpes simplex virus 1

Sidra Saeed
FA08-BBS-015
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 Symptoms
Classification
 Diagnosis
Discovery of HSV
 Treatment
Types of HSV
Viral Structure
Complications
Hosts of HSV
Mode of Replication
Virus Latency
Modes of Transmission
Immune Response against HSV
Group: (dsDNA)
Family: Herpesviridae
Subfamily: Alphaherpesvirinae
Genus: Simplexvirus
Species: Herpes simplex virus 1 (HSV-1)
• HSV is an ancient disease with descriptions of
orolabial herpes appearing in records from the
fifth century BCE.
• In the 1736 Astruc (physician to King of France)
identified Herpes as a cause of genital infection.
• Over the next 50 years many different strains of
herpes were discovered.
• In 1893 intimate human-to-human transmission
was identified.
• Finally neonatal HSV infection was identified in
• The Type 1 virus
causes cold sores.
Most people get Type
1 infections during
infancy or childhood.
• The Type 2 virus
causes genital sores.
Most people get Type
2 infections
following sexual
contact with an
infected person.
Both types can be differentiated by biologic, biochemical and antigenic properties
• Composed of a dsDNA
(152kbp) nucleoprotein core
• Core is surrounded by an
icosahedral protein capsid
• 100nm capsid is enclosed in an
outer envelope consisting of at
least 8 glycoproteins.
• The tegument is present
between the capsid and the
envelope
• Envelope spikes ~8 nm long
• The virus requires a moist
environment for survival.
 Meningitis: infection of the sheaths and membranes
(meninges) covering the brain and the spinal cord.
 Encephalitis: acute inflammation of the brain,
commonly caused by a viral infection by insect bites or
food and drink
 Eczema herpetiform: widespread herpes across the
skin)
 Keratoconjunctivitis: Infection of the eye
 Prolonged, severe infection in immunosuppressed
individuals
 Pneumonia
 Infection of the trachea
• Humans
• Simians
• Cattle
• Cats
• Chickens
Of these, only herpes virus simiae is harmful to us.
• The viral envelop becomes incorporated in the
host’s membrane
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The nucleocapsid uncoats and releases the DNA into the
nucleus.
• In the nucleus the DNA circularizes, and the host’s
enzymes begin to transcribe the first set of viral
genes, known as early genes
• The early mRNA molecules enter the cytoplasm,
where they are translated into the early proteins.
• The early proteins, in turn, enter the nucleus for
viral DNA replication
• At this point, the cell begins to transcribe late
mRNA molecules
• These mRNAs enter the cytoplasm for the
translation of late proteins
• The late proteins include the capsid structural
proteins, which enter the nucleus
• The late proteins also include envelop proteins,
which are produced in ER.
• These envelop proteins become incorporated
in the nuclear membrane
• The viral DNA continues to replicate.
• During this later stage of replication
concatemers of viral DNA form.
• These copies are cut into individual genomes
as they are packaged into capsids
• At the nuclear membrane, capsid and the
DNA bud off and become surrounded by
membrane material with embedded
membrane proteins
• The virus passes through the ER and buds off
this membrane before migrating to the plasma
membrane
• The virus fuses with the plasma membrane
and is released from the cell.
 HSV is transmitted through the body on nerves
or synapses to and from mucosal tissues
 Vaccines and antiviral medicines can’t attack latent virus
 Once infected, a person is infected for life.
 Latency in mucosal surfaces is effective way to transmit
because of common mucosal contact
•Direct skin-to-skin contact with the infected areas
• Sexual Intercourse
• Oral Sex
Even though most skin on our bodies is too thick for the virus to
penetrate, it can penetrate areas with mucous membranes such as
the genitals, the mouth, the esophagus, the trachea, and even onto
broken areas of skin anywhere
The constant battle between our body and invaders…
Both the cellular and humoral arms of the immune response are involved
Interferon and natural killer cells are important in limiting the initial infection .
Cytotoxic T cells and macrophages kill infected cells
The humoral response (antibodies against surface glycoproteins) leads to
neutralization.
The virus can escape the immune system by coating itself with IgG via Fc
receptors
The virus can also spread from one cell to another without entering the
extracellular space and coming in contact with humoral antibodies
Cell-mediated responses are vital in controlling herpes infections.
 Mouth sores
 Genital lesions
 Blisters and/or ulcers
 Fever
 Enlargement of lymph
nodes
• The appearance of HSV is often so typical.
• The genital herpes sores may not be visible to the
naked eye
• A viral PCR can be run on a swab of infected
tissue.
• A blood test, can show if a person has been
infected with HSV but cannot distinguish between
type I and II.
• There is no vaccine that prevents this disease
from occurring.
• Oral anti-viral medications such as
• acyclovir (Zovirax),
• famciclovir (Famvir),
• or valacyclovir (Valtrex)
have been developed to effectively treat
herpes infections.
• To keep from spreading the infection:
Keep the infected area clean and dry to prevent
other infections from developing.
Try and avoid touching the sores.
Wash your hands after contact with the sores.
Avoid sexual contact from the time you first feel
any symptoms until the sores are completely
healed.
HUMAN
PAPILLOMA
VIRUS
DISCOVERY
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Discovered by Dr Harald Zur Hausen in
1984 in German Cancer Research Centre.
Was found in the tumorous cells associated
with cervical cancer patients.
A group of viruses containing almost 150
different types of viruses.
Double stranded DNA viruses.
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BACKGROUN
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Papilloma viruses are known to infect
almost all mammallian and avian species
having 100 types infecting humans
Specific types infect human skin and
mucosal epithelium to cause papillomas or
warts
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Mucosal types of infection is found in
persons having sexual contact with HPV
infected women and homosexual males
Most of the infection caused by this are
mostly cleared by the immune system
before showing any symptoms
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More than 5% of cancers worldwide are
caused by infection from this virus
The most common sexually transmitted virus
afflicting 50-80% population
Of the 100 known types; 40 infect the genital
tracts
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REPLICATION
HPV infection is limited to the basal cells
associated with stratified epithelium
These are the only tissues in which they can
replicate
In case of any abrasion to epithelium it comes
in contact with the basement membrane cells
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Its infection process is slow taking 12-24
hours of transcription initiation
HPV virus does not show cytolytic activity
Rather the virus particles are released in the
form of degeneration of desquamating cells
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This virus can survive for many months
without a host at low temperatures , so it
can be spread if an infected person walks
bare-foot
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VIRAL
REPLICATION
HPV has 6 early proteins(E1,E2,E3,E4,E5,E6)
and 2 late proteins (L1,L2)
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Before integrating in host genome
High levels of E1 & E2
E2 repress E6/E7 expression
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After integrating in host
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E2 function disrupted
Prevents repression of E6/E7
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ONCOGENES
Role of E6 & E7 proteins in cancer
E6 inactivates p53 TSP whereas E7 inactivates
pRb TSP
These proteins modify the host cell cycle
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to keep differentiating the keratinocytes
helps in the amplification of viral genome
replication
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ROLE of E6
Protein
E6 forms association with E6 associated
protein of host
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Ubiquitinate the p53 protein
cause proteosomal degradation of p53
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ROLE OF E7
PROTEIN
E7 acts as primary transforming protein
– Competes for retinoloblastoma protein
binding
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Freeing the transcription factor E2f to
transactivate its target pushing cell cycle
forward
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LATE
PROTEINS
L1&L2
These are structural proteins that
encapsidate the viral genome
Once the genome is encapsidated it
undergoes the assembly/maturation event
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Stabilizes the virions
Increases viral specific infectivity
Virions can then be sloughed off as squames
from host epithelium and viral life cycle
continues
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TRANSMISSIO
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Prenatal
– Genital HPV are usually transmitted from
mother to newborn
Perinatal
Perinatal transmision of HPV type 6 and 11
causes onset of juvenile-onset recurrent
respiratory papilllomatosis(JORRP)
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Genital
transmission is from infected partner
during sexual contact
it can not be prevented even using
condoms
because some of the infected region is
SYMPTOMS
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COMMON WARTS
rough, raised bumps that usually occur on the
hands, fingers or around fingernails.
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Plantar Warts
hard, grainy growths that usually appear
on the heel or ball of your feet, areas that
feel the most pressure. These warts may
cause discomfort or pain
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FLAT WARTS
Flat-topped, slightly raised lesions darker
than your regular skin color. They usually
appear on your face, neck, hands, wrists,
elbows or knees.
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GENITAL WARTS
Flat lesions, small cauliflower-like bumps
or tiny stem-like protrusions.
VACCINES FOR HPV
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Gradasil
Work against HPV
16&18 which cause 70%
of cervical cancer
HPV 6&11 which
cause 90% of genital warts
Work
against HPV
• CERVARIX
16&18 which cause
70% of cervical cancer
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ScienceDaily (Oct. 6,
2008);
http://www.sciencedail
y.com/releases/2008/1
0/081006093031.htm
Ganguly, N.; Parihar,
S. P. (2009). "Human
papillomavirus E6 and
E7 oncoproteins as
risk factors for
tumorigenesis".