Transcript Herpes Simplex Virus (HSV)

HERPESVIREDAE
Introduction
• The word herpesvirus is derived from the Greek
herpein, meaning to creep.
• The order Herpesvirales currently consists of 3 families,
3 subfamilies, 17 genera, and > 90 species.
• Herpesviruses found in mammals, birds, and reptiles
constitute the family Herpesviridae.
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Herpesviruses That Infect Humans
Genus
(HSV 1 or 2)
(VZV)
(CMV)
(HHV)
Genus
(EBV)
Genus
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Introduction
• A notable characteristic of herpesviruses is that, once
they have infected a host, they commonly remain as
persistent infections for the lifetime of the host.
• These infections are often latent infections, which can
be reactivated from time to time, especially if the host
becomes immunocompromised.
• Both primary and reactivated herpesvirus infections can
either be asymptomatic or can result in disease of
varying severity.
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Major Characteristics
• Herpesviruses are DNA
viruses.
• DNA is linear and double
stranded.
• Their diameter ranges from
120 to 200 nm.
• They are enveloped.
• Their capsid is icosahedral
composed of 162
capsomeres.
An electron micrograph of HSV
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Replication
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Attachment to the host cell
Fusion of viral envelope with the cell
membrane
Uncoating
DNA migrates to host cell nucleus
Transcription, mRNA migrates to the
cytoplasm for translation, proteins
migrate to the nucleus
Replication to yield many genomes
Assembly takes place in nucleus
Virus envelope is derived from the
nuclear membrane
Transport to the outer cell
membrane and release
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1&2
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1&2
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Herpes Simplex Virus (HSV)
• There are two distinct herpes simplex
viruses:
• Type 1 and type 2 (HSV-1, HSV-2)
• They differ in their mode of transmission.
• HSV type 1 (Human herpes virus type 1
or HHV type 1) is usually isolated from
lesions in and around the mouth and is
transmitted by direct contact or droplet
spread from cases or carriers.
• HSV type 2 (HHV type 2) is transmitted
sexually or from a maternal genital
infection to a newborn.
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Herpes Simplex Virus (HSV)
• Epidemiology
• Herpes simplex types 1 and 2 are found worldwide, only in
humans.
• Herpes simplex type 2 has traditionally been associated with
genital herpes, and type 1 with oral herpes, but type 1 is
believed to cause 20–25% of genital herpes cases.
• Seroprevalence of HSV-1 worldwide is about 90%, although in
developed countries it is below 70%.
• HSV-2 has a seroprevalence of about 25% in some developed
countries.
• It is believed that HSV-2 seroprevalence is lower than for
HSV-1 because of partial protection supplied by an initial
HSV-1 infection
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Herpes Simplex Virus (HSV)
• Transmission
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Saliva,
Vaginal secretions,
Secretions from blisters in oral and anogenital tracts
Eyes; skin lesions
Herpes simplex virus type 1:
• mainly oral;
• Herpes simplex virus type 2:
• mainly sexual
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Herpes Simplex Virus (HSV)
• Pathogenesis
• The mechanisms involved in the pathogenesis of HSV-1 and HSV-2
are very similar.
• Both viruses initially infect and replicate in mucoepithelial cells and
then establish latent infection in neurons.
• Skin and mucous membranes are the portals of entry in which the
virus also multiplies, causing lysis of cells and formation of blisters .
• Soon after replication is under way in
the skin or a mucous membrane,
virions travel to the root ganglia via
the sensory nerves supplying the area.
• The virus then becomes latent in the
ganglia.
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Herpes Simplex Virus (HSV)
• Clinical Features
• Gingivostomatitis; vesicles on the
gums and oral mucosa, break down
to form ulcer
• Eczema herpeticum
• Keratoconjunctivitis
• Meningitis and encephalitis
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Herpes Simplex Virus (HSV)
• Laboratory Diagnosis
• Cell culture in human diploid cells: CPE
may include foci of enlarged cells, some
of which are multinucleated.
• Stained smears of an active lesion often
reveal multinucleated cells containing
intranuclear inclusions.
• Detection of antibodies (ELISA)
• Polymerase chain reaction is useful for
detecting viral DNA in cerebrospinal
fluid when herpetic infection of the CNS
is suspected
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Herpes Simplex Virus (HSV)
• Control and Treatment
• Vaccination (split vaccine), an experimental one.
• Acyclovir is the drug of choice.
• It inhibits viral DNA polymerase
• Idoxuridine, a nucleoside analogue
• for ophthalmic infection, topical
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Varicella-Zoster Virus (VZV)
• Subfamily: Alphaherpesviruses
• Genus: Varicellovirus
• Species: Varicella-zoster virus
• Causes chickenpox (varicella) and, with recurrence,
causes herpes zoster or shingles.
• Varicella (chickenpox) and herpes zoster are different
manifestations of the same virus infection.
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Varicella-Zoster Virus (VZV)
• Characteristics of the Virus
• Varicella-zoster virus is
morphologically identical
to herpes simplex virus.
• It can be grown in cultures of
human fibroblasts or HeLa cells.
• Cytopathic changes are more focal
and spread much more slowly than
those induced by HSV
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Varicella-Zoster Virus (VZV)
• Transmission
• Aerosol
• At risk
• Immunosuppression
• Distribution
• Worldwide
• No seasonal incidence
• Vaccines or antiviral drugs
• Attenuated vaccine
• Antiviral drugs: acyclovir, foscarnet
• DNA polymerase inhibitors
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Varicella-Zoster Virus (VZV)
• Varicella (chickenpox)
• Varicella (chickenpox) is one of the mildest highly
communicable and most common of childhood infections.
• It is usually a mild disease of childhood and is normally
symptomatic, although asymptomatic infection may occur.
• The portal of entry of the virus is the respiratory tract or
conjunctiva.
• After an incubation period of about two weeks (7–23 days) the
lesions begin to appear
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Varicella-Zoster Virus (VZV)
Varicella (chickenpox)
• In children, there is little prodromal
illness and the disease is first noticed
when skin lesions appear.
• The rash is mainly affecting the trunk,
and is very superficial without
involving the deeper layers of the skin.
• The rash appears in successive crops, so
that all stages of the eruption can be
seen at the same time.
• It matures very quickly, beginning to
crust within 48 hours.
• Recovery is usually uneventful.
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Varicella-Zoster Virus (VZV)
Varicella (chickenpox)
• Complications
• Primary infection is usually more severe in adults than in
children.
• The rash may become hemorrhagic.
• Varicella pneumonia is more common in adults.
• A variety of organs may be affected with complications like
myocarditis, nephritis, meningitis and encephalitis.
• Secondary bacterial infections.
• Reyes’ syndrome may follow varicella in some cases with a
history of administration of salicylates.
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Varicella-Zoster Virus (VZV)
Herpes Zoster (Shingles, zona)
• While varicella is typically a disease of childhood, herpes
zoster is one of old age.
• Herpes zoster usually occurs in persons who had chickenpox
several year earlier.
• The virus remaining latent in the sensory ganglia, may leak
out at times but is usually held in check by the residual
immunity.
• It is believed that years after the initial infection, when the
immunity has decreased, the virus may be reactivated, travel
along the sensory nerve to produce zoster lesions on the area
of the skin or mucosa supplied by it.
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HERPES ZOSTER (SHINGLES, ZONA)
• Complications
• Postherpetic pain: In the affected area is frequent,
particularly in the elderly.
• Ophthalmic zoster
• Generalized zoster
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HERPES ZOSTER (SHINGLES, ZONA)
• laboratory diagnosis
• Diagnosis is usually clinical.
• Microscopy: Multinucleated giant cells
• Direct examination by electron microscopy will reveal herpes
particles.
• Virus isolation
• Virus antigen: The virus antigen can be detected in scrapings from
skin lesions by immunofluorescence
• ELISA and PCR techniques are also in use.
• Serological diagnosis: A rise in specific antibody titer can be
detected in the patient’s serum by various tests, including latex
agglutination, and ELISA.
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HERPES ZOSTER (SHINGLES, ZONA)
• Prophylaxis and treatment
• Active Immunization
• Attenuated vaccine
• Passive Immunization
• Varicella-zoster immunoglobulin (VZIG) seems to be of
some use in preventing or modifying severe disease in
immunodeficient patients.
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CYTOMEGALOVIRUS (CMV), HHV 5
• Cytomegaloviruses (CMV), formerly known as salivary
gland viruses, are a group of ubiquitous herpesviruses of
humans and animals.
• Cytomegalovirus (CMV) means ‘large cell virus’ and it
refers to the swollen cells which contain large
intranuclear inclusions that characterize this viral
infection.
• Following primary infection, the virus can remain in a
latent form in secretory glands, lymphoreticular tissue,
kidney and other tissue and may reactivate at any time.
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CYTOMEGALOVIRUS (CMV), HHV 5
• Epidemiology
• Transmission
• Blood, tissue and body secretions (urine, saliva, semen, cervical
secretions, breast milk, tears)
• At risk or risk factors
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Babies whose mothers become infected during pregnancy
Sexual activity
Transplant recipients
Immunosuppression
• Distribution
• Worldwide
• No seasonal incidence
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CYTOMEGALOVIRUS (CMV)
• Pathogenesis
• Infects epithelial and other cells
• Mainly causes subclinical infections
• Latent infection in CD34+ bone marrow progenitor
cells (differentiate into all the various blood cell
types).
• Immunosuppression leads to recurrence and severe
disease
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CYTOMEGALOVIRUS (CMV)
• Laboratory diagnosis
• Specimens: CMV can be isolated from the urine, saliva, breast milk,
semen, cervical secretions and blood leucocytes.
• Demonstration of cytomegalic cell: The histologic hallmark of
CMV infection is the cytomegalic cell, which is an enlarged cell that
contains a dense, central, “owl’s-eye,”
• Isolation of virus
• DNA probes: DNA probes are used to directly detect the CMV
antigens in tissues or fluids.
• Polymerase chain reaction (PCR): To directly detect the genome in
tissues or fluids.
• Serology: IgM antibodies suggests a current infection and can be
detected in serum by ELISA.
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CYTOMEGALOVIRUS (CMV)
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CYTOMEGALOVIRUS (CMV)
• Treatment and Prevention
• Ganciclovir and foscarnet have been approved for the
treatment of CMV infections.
• Screening of blood and organ donors and administration of
CMV immunoglobulins have been employed in prevention.
• No vaccine is available
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Epstein-Barr Virus (EBV),HHV 4
• Epstein–Barr virus (EBV) is in some respects the most
sinister herpesvirus, for its association with malignant
disease is now well established.
• Mainly human B cells have receptors for the virus.
• EBV infected B cells are transformed so that they
become capable of continuous growth in vitro.
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Epstein-Barr Virus (EBV)
• Epidemiology
• Epstein-Barr virus (EBV) infection is common amongst people
living in developing countries.
• Children are subclinically infected early in life.
• In developed countries, infection generally occurs in early adulthood
and infected individuals may present with infectious mononucleosis.
• Infection is mostly acquired by the oral route “kissing disease”.
• Evidence of sexual transmission and transmission during blood
transfusion and organ transplantation have been noted.
• Transmission
• Saliva, close oral contact, or shared items (cup or toothbrush)
• Vaccines
• No vaccine against EBV is currently available.
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Epstein-Barr Virus (EBV)
• Pathogenesis
• EBV infects and results in lysis of oropharyngeal epithelial cells,
from where it may spread to passing B-cells in the associated
lymphoid tissue.
• B-lymphocytes are infected and immortalised by the virus, resulting
in a state of polyclonal activation.
• Most of the B-cells remain latently infected for life, while a small
percentage may undergo a lytic infectious cycle.
• The infection is controlled by an intact cellular immune response
where cytotoxic T-cells play a pivotal role.
• Memory B-cells are the main reservoirs for EBV reactivation and for
the development of virus-related malignancies.
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Epstein-Barr Virus (EBV)
• Clinical conditions
1. Infectious mononucleosis
2. EBV associated malignancies:
a) Burkitt’s lymphoma
b) Nasopharyngeal carcinoma
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Epstein-Barr Virus (EBV)
1. Infectious Mononucleosis (Glandular Fever)
• This is an acute self-limited illness usually seen in
nonimmune young adults.
• The incubation period is 4–8 weeks.
• Infectious mononucleosis is characterized by high fever,
malaise, pharyngitis, lymphadenopathy (swollen glands),
and, often, hepatosplenomegaly.
• A mild transient rash may be present.
• Some patients treated with ampicillin may develop a
maculopapular rash due to immune complex reaction to the
drug.
• The typical illness is self-limited and lasts 2–4 weeks.
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Epstein-Barr Virus (EBV)
• Laboratory Diagnosis
• Hematological findings & Serological tests:
• Leukocyte count (20x109/liter, 50% are lymphocytes, 20% are atypical)
• T-cells react against viral antigens on B-cells and kill them
• Heterophile antibodies:
• B-cells transformed by EBV undergo polyclonal expansion, they produce
antibodies with a number of specificities,
• e.g., one is directed against ampicillin,
• others agglutinate sheep or horse RBC
• Specific antibodies:
• Antibody to EA (early antigen) indicates current or recent infection as
does IgM antibody to VCA (viral capsid antigen) whereas, IgG antibody
to VCA is evidence of past infection.
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Epstein-Barr Virus (EBV)
1. Infectious Mononucleosis (Glandular Fever)
• Complications
• They are rare but some
are serious:
• Acute airway obstruction
• Splenic rupture
• Neurological complications
include meningitis and
encephalitis
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Epstein-Barr Virus (EBV)
EBV associated malignancies: a) Burkitt’s lymphoma
• Epstein–barr virus (EBV) is associated
with the development of Burkitt’s
lymphoma (a tumor of the jaw in
African children and young adults).
• Most African tumors (>90%) contain
EBV DNA and express EBNA1
antigen.
• Malaria, a recognized cofactor.
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Epstein-Barr Virus (EBV)
EBV associated malignancies: b) Nasopharyngeal
Carcinoma
• This cancer of epithelial cells is
common in males of Chinese origin.
• It mainly affects people aged 20–50
years, majority are males.
• EBV DNA is regularly found in
nasopharyngeal carcinoma
(NPC) cells.
• Genetic and environmental factors are
believed to be important in the
development of nasopharyngeal
carcinoma
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