Download Human Herpesviruses Lecture Objectives

Human Herpesviruses
Jackie Parker, Ph.D.
Department of Pediatrics, Infectious Diseases
CHB 118B, 1600 6th Avenue South
(behind Children’s Hospital)
996-7881 (office)
996-7875 (lab)
[email protected]
Lecture Objectives
• Introduction to the Human herpesviruses
• Virus replication
• Human herpesviruses
 Herpes Simplex Viruses
 VZV
 EBV
 CMV
 HHV6,7,8
 Simian B Virus
*Clinical manifestations
*Antiviral treatment
*Disease in the Immunocompromised host
1
Herpesviruses: History
• Herpes infections have
been described since
ancient Greece
• Name derived from the
Greek word “herpein”, which
means “to creep”
• Hippocrates and other
Greek scholars used the
word “herpes” to describe
spreading cutaneous
lesions caused by many
types of herpesviruses
Herpesviruses: General Features
Family
Herpesviridae
Subfamilies
Alpha, Beta, Gamma
herpesvirinae
Size
180-200 nm
Envelope
Yes
Genome
linear ds DNA
ranges from ~120 kb (VZV)
to ~230 kb (CMV)
Genome
Replicated
Virus
Assembly
nucleus
nucleus
2
Herpesviruses:
Structural Components
 Viral glycoproteins, found
embedded within the lipid
envelope, are responsible for
several functions, including
receptor-mediated cellular entry.
 The tegument, a layer of
proteins between the envelope
and the underlying capsid.
Tegument proteins are
responsible for induction of viral
gene expression and shutoff of
host protein synthesis
immediately following infection,
in addition to virion assembly
functions.
 Icosadeltahedral capsid
 dsDNA core
Herpesviridae Subfamilies
Alphaherpesvirinae (HSV-1, HSV-2, VZV)
-variable host range
-short reproductive cycle; rapid spread in culture
-capacity to establish latent infections primarily (but not
exclusively) in sensory ganglions
Betaherpesvirinae (CMV, HHV-6)
-restricted host range
-long reproductive cycle; slow infection in culture
-latent virus maintained in secretory glands, lymphoreticular
cells, kidneys, and other tissues
Gammaherpesvirinae (EBV)
-members replicate in lymphoblastoid cells
-latent or lytic infection, but without production of infectious
progeny
3
Gene organization among representative herpesviruses
(HSV)
α
(VZV)
(HCMV)
β
(HHV-6B)
γ
(EBV)
(HHV-8)
Properties of Human Herpesviruses
Common Name
(Designation)
Target cell type
Latency
Disease
HSV-1 (HHV-1)
Mucoepithelia
Neuron
Oral, ocular lesions;
HSV-2 (HHV-2)
Mucoepithelia
Neuron
Genital, ocular, disseminated
Varicella Zoster virus, VZV
(HHV-3)
Mucoepithelia
Neuron
Chicken pox, shingles
Epstein-Barr virus, EBV
(HHV-4)
B lymphocyte,
epithelia
B lymphocytes
Infectious mononucleosis,
Cytomegalovirus (CMV)
Epithelia,
monocytes,
lymphocytes
Monocytes,
lymphocytes,
dendritic cells
numerous
(HHV-5)
Herpes lymphotrophic
virus (HHV-6)
T lymphocytes and
others
T lymphocytes
and others
Roseola in infants
HHV-7
T lymphocytes and
others
T lymphocytes
and others
Some cases of roseola,
possibly Pityriasis rosea
HHV-8. Kaposi’s sarcoma
associated virus (KHSV)
B cells,
Endothelial cells
B lymphocytes,
others?
Tumors, Kaposi’s sarcoma,
some B cell tumors
Simian B virus (Herpes B)
Mucoepithelia
Neuron*
encephalitis
encephalitis, etc.
tumors
4
HHV Infections in the
Immunocompromised Patient
 In immune competent patients any clinical illness tends to be mild and self-limiting.
 HHVs cause severe and atypical clinical illness in immunocompromised patients.
 Patients may be immunocompromised for many different reasons, most of which are
acquired rather than congenital. These include:
 Iatrogenic - the consequence of prescribed drugs such as corticosteroids or other
immunosuppressants.
 Cancer - often associated with dysregulation of the immune system.
 Infection - patients with T-cell immunodeficiency (e.g. AIDS) generally have more
severe and persistent HHV infections.
 It is also important to remember that the immune system changes through life:
 Neonates have an immature immune system and are particularly susceptible to
severe HHV primary infection that may be fatal.
 Primary HHV infection in pregnancy can be severe
• HHV infection of the developing fetus can cause severe congenital
abnormalities associated with mortality and high morbidity.
• Pregnant women are at increased risk of developing severe primary HHV
infection that can be fatal.
 The immune system becomes less efficient with increasing age.
• In particular, T-lymphocyte immunity is less effective in old age.
Alpha herpesviruses
•
Herpes simplex virus type 1 (HSV-1)
•
Herpes simplex virus type 2 (HSV-2)
•
Varicella Zoster virus (VZV)
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Herpes Simplex Viruses
(HSV-1, HSV-2)
• HSV-1 and HSV-2 are neurotrophic alpha-herpesvirus
that only naturally occur in humans. There are no
animal reservoirs.
• Significant differences between genomes of HSV-1
and HSV-2, but both cause similar clinical illnesses
• HSV-1 mostly infects oral mucosa, but can infect
genital mucosa, whereas HSV-2 mostly infects
genital mucosa, but can infect oral mucosa
• HSV-1 seroprevalence exceeds 90%, whereas HSV-2
seroprevalence is ~18%.
Herpes Simplex Viruses,
cont.
• Initially establish a productive infection in epithelial
cells, gain access to the sensory nerve endings within
the infected area, and travel by retrograde axonal flow
to neuronal cells bodies within the respective dorsal
root ganglia
• Can establish a latent infection within sensory neurons
and lytic replication in the nervous system is generally
limited
• Reactivates periodically in a fraction of the latently
infected neuronal cells
• The newly replicated virus is transported anterograde,
usually to a site at or near the portal of entry into the
body, where it may cause a localized lesion
6
ab

UL
b’a’a’c’
 
US
ca

Herpes simplex virus genome

The "a" sequences are important in both circularization of the viral DNA, and in
packaging the DNA in the virion.

The 9,000 bp long repeat (red), which encodes 4 proteins, including an important
immediate early regulatory protein (α0). Also includes the promoter of and most of
the "gene" for the latency associated transcript (LAT).

The long unique region (UL),108 kb long, encodes at least 65 distinct proteins
(actually more because some ORFs are spliced and expressed in redundant ways).
It contains genes for the DNA replication enzymes and the capsid proteins, as well
as many other proteins.

The 6,600 bp short repeats (yellow) encodes a transcriptional activator (α4) that
acts along with α0 and α27 (in the UL) to stimulate the infected cell for all viral gene
expression that leads to viral DNA replication.

Three origins of replication: the oriL is in the middle of the UL region, while the oriS
is located within the repeat sequences and thus, is present in two copies.

The 13,000 bp unique short region (US) encodes 14 ORFs, a number of which are
glycoproteins important in viral host range and response to host defense.
Herpesvirus Replication (1)
• Initial attachment is mediated by the interaction of viral envelope
glycoproteins with cell surface receptors.
• Tropism of some herpesviruses (e.g. EBV) is restricted as a result of
the tissue-specific expression of their receptors.
• The nucleocapsid is released into the cytoplasm through fusion of
the viral envelope and plasma membrane.
• Virally encoded enzymes and transcription factors are carried into
the infected cell in the tegument of the virion.
7
Herpesvirus Replication (2)
•The nucleocapsid docks with the nuclear membrane and delivers the viral
genome into the nucleus, the site of viral gene transcription and replication.
•VP16, a structural viral protein, in conjunction with cellular proteins Oct-1
and complex forming factor (CFF), interacts with sequence-specific
elements within the promoters of five immediate early (IE) (alpha) genes:
ICP0, ICP4, ICP22, ICP27 and ICP47.
•Transcription of the viral genome and viral protein synthesis proceeds in a
coordinated and regulated manner in the following three phases:
•Immediate early proteins(α genes), which are necessary for the regulation of
gene transcription and takeover of the cell
•Early proteins (β genes), includes more transcription factors and enzymes,
including the DNA polymerase
•Late proteins (γ genes), which includes the viral structural proteins
http://www.dbc.uci.edu/~faculty/wagner/hsvresrch.html
Herpesvirus Replication (3)
 The viral genome is transcribed by the cellular DNA-dependent
ribonucleic acid (RNA) polymerase and is regulated by viral
encoded and cellular nuclear factors.
 The interplay of these factors determines whether the proteins
necessary for a lytic, persistent or latent infection are produced.
8
Latency: HSV-1 and HSV-2
• The virus establishes latency in sensory neurons.
• Some neurons harboring latent virus express an
RNA designated as Latency Associated Transcript
(LAT).
• This RNA does not play a role in the establishment
or maintenance of the latent state.
• Viral proteins have not been demonstrated in
neurons harboring latent virus.
• DNA is maintained in episomal form (circular nonintegrated)
• Establishment of latency may involve a cellular
function.
Reactivation from latency
• Not all neurons harboring virus reactivate at once.
• Reactivation is more frequent than the appearance
of clinical lesions: the phenomenon is known as
“shedding” which may occur in a significant fraction
of infected individuals.
• The stimulus for reactivation may differ from one
individual to another: e.g., fever, physical, emotional
stress, intake of hormones, menstruation, etc.
Immunosuppression exacerbates the lesions caused
by reactivated virus.
• Upon reactivation, the virus multiplies in the sensory
neuron and is transported to a site at or near the
portal of entry. On rare occasion, the reactivated
virus causes ocular or CNS infections.
9
HSV-1 and HSV-2: Establishment
of Latency and Reactivation
Clinical Manifestations of
Herpes Simplex Infections
10
Diseases
Caused
by Herpes
Oral
HSV
Simplex Viruses
• Orolabial herpes (almost all type 1)
 Primary – HSV gingivostomatitis
 Recurrent – herpes labialis (cold sores, fever blisters)
• Ocular infections
• Cutaneous herpes
• Genital herpes (mostly type 2)
 Primary
 Recurrent
• Herpes proctitis, perianal herpes (type 2)
• HSV encephalitis
Diseases
Caused
by Herpes
Oral
HSV
Simplex: Orolabial
•
•
•
•
Mostly caused by HSV-1
In primary herpetic gingivostomatitis, typical clear lesions first
develop, followed by ulcers with white appearance
Infection initially on the lips and spreads to all parts of the mouth
and pharynx
Spectrum of severity of clinical illness ranging from a few intraoral
ulcers and no systemic features, to severe oral ulceration. Clinical
symptoms include:
 Painful vesicles that burst to leave ragged ulcers
 Drooling, from increased saliva production due to inflammation
 Systemic symptoms including fever, cervical lymphadenitis, etc.
•
Risk of autoinoculation to other sites (eye, skin) highest during the
acute phase of the primary infection
 Herpetic whitlow
 Herpetic keratitis
•
Disease is more severe in immunosuppressed people
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Diseases Caused by Herpes
Simplex: Orolabial (2)
• HSV-1 latency in trigeminal ganglia
• Reactivation triggers include: UV exposure,
fever, menses, trauma, etc.
• Reactivation from trigeminal ganglia often
results in cold sore development at or near
initial site of infection
• prodrome of itching, tingling; cluster of
painful vesicles
• External lesions
• Lips (90%)
• Nose, chin, or cheeks (10%)
• Intra-oral lesions can also occur
Diseases
Caused
by Herpes
Oral
HSV
Simplex Viruses: Oral
Herpes simplex cold sore
Gingivostomatitis in
an AIDS patient
Herpetic gingivitis
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Herpes Labialis:
Epidemiology in the US
• Cold sores affect 1 in 5 people
• ~98 million cases each year
• 35%-60% Caucasians: HSV-1 serology +
• Seroprevalence dependent on age, socioeconomic
status, and geographic location
• Primary infection occurs almost exclusively before
age 4
 Usually asymptomatic
• 20%-40% of individuals have recurrent outbreaks
 In only 1% recurrence is severe
Herpes Labialis – Principles Of
Antiviral Treatment
• Treat early (during prodrome) – rapid natural
evolution of disease
• Short duration of therapy – period of viral
replication is brief (2-3 days), then controlled
by host immunity
• High dose systemic therapy – deliver high
drug concentrations to tissue, prevent
extension of HSV to uninfected cells
Ref: Spruance et al, J infect Dis 161:185, 1990
13
Topical Antiviral Therapy
for Herpes Labialis
• Penciclovir 1% cream (Denavir®)




Reduced duration of lesion pain
Accelerated lesion healing
Apply topically q2h
FDA approved September, 1996
• Acyclovir 5%
 In PEG ointment – not effective
 In MAC cream
Diseases Caused by Herpes
Simplex Viruses: Whitlow
• Direct contact with body
secretions
• Infection occurs through small
cuts or abrasions on the fingers,
hand or wrist
• HSV-1 or HSV-2
• Often seen in health care
workers treating patients with
HSV infections
• Thumb-sucking children are also
more susceptible
Herpetic whitlow
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Diseases Caused by Herpes
Simplex Viruses: Bell’s Palsy
• Acute onset of unilateral
facial nerve palsy
• Multiple causes; many of
the “idiopathic” cases may
be associated with HSV
reactivation
• Small studies with
prednisone and/or
acyclovir have yielded
variable results – larger
studies ongoing
• Many experts recommend
valacyclovir + prednisone
– optimal dose & duration
not known
Diseases Caused by Herpes
Simplex Viruses: Encephalitis
• Reactivation of HSV-1; 1250 cases/yr in US of HSE
• Presentation: AMS, fever, HA, personality change, seizures
• Diagnosis: MRI – temporal lobe lesion
CSF – PCR for HSV DNA
• Therapy: Acyclovir 10-15 mg/kg q8h x 21d
• Outcome (with therapy): mortality 13% at 1 mo., 28% at 18 mo,
38% have no/mild impairment at 6 mo
15
Diseases Caused by Herpes
Simplex Viruses: Genital Herpes
• Mostly likely caused by HSV-2
• 18-20% of US population is HSV-2 seropositive
• Primary infection may be more severe, may be
associated with systemic syndromes, or may be
asymptomatic.
• Variable frequency of recurrences – about 90%
will have at least 1 recurrence/year
• Vesicles/ulcerations on genitals or perigenital
skin
• Key to natural history – asymptomatic viral
shedding
Antiviral Therapy for
Primary Genital HSV
•
•
•
Acyclovir 200 mg po 5x daily for 10 days
Valacyclovir 1000 mg po bid for 10 days
Famciclovir* 125 mg po tid for 10 days
*not FDA approved for this indication
16
Oral HSV
Diseases Caused
by Herpes Simplex
Viruses: Ocular Infections
• HSV-1 usually associated with ocular infections
• Leading cause of blindness in the United States
• Typically is limited to one eye
• A number of manifestations, including blepharitis,
conjunctivitis, keratis, retinitis
• Long-term (12 month) suppressive therapy with an
oral antiviral drug (acyclovir) reduces rates of
recurrence of HSV keratitis and rates of recurrence
of ocular complications
Oral HSV
Diseases Caused
by Herpes Simplex
Viruses: Ocular Infections
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Antiviral Drugs
All anti HSV drugs currently licensed
are dependent on being activated by
viral enzymes.
Herpes Simplex Viruses:
Antiviral Therapy and Drug Resistance
nucleoside analogs
Drugs are activated by a viral enzyme, thymidine kinase
Only activated in herpes-infected cells, few side effects as a
consequence.
The best known nucleoside analog used to treat herpes simplex
virus infections is acycloguanosine (acyclovir); other approved
drugs include famciclovir and valacyclovir.
Drug resistant herpes mutants do arise with all of these, although
resistant strains are usually less virulent than the wild type.
Drugs act only against replicating virus (incorporated into DNA
during synthesis); are ineffective against latent virus.
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Herpes Simplex Viruses:
Antiviral Therapy and Drug Resistance
acyclovir
acyclo GMP
acyclo GTP
Herpes Simplex Viruses:
Antiviral Therapy and Drug Resistance
Mechanisms of Action of Acyclovir:
Inhibition of DNA Synthesis & Chain
Termination
19
Activation of acyclovir (ACV) and
gancyclovir (GCG) by viral enzymes
Anti-CMV drugs
Anti-HSV drugs
DNA
DNA
Inhibits
polymerase
GCG-TP
Inhibits
polymerase;
DNA terminator
ACG-TP
ACG-DP
GCG-DP
ACG-MP
GCG-MP
GCG
Viral
protein
kinase
Viral
Thymidine
kinase
ACG
Wide substrate
range
Varicella-Zoster Virus (VZV)
• Primary infection causes chickenpox (varicella)
• Reactivated virus causes herpes zoster, or
shingles
• Spreads primarily through the respiratory route
• Local replication occurs in respiratory tractleads to formation of skin lesions over the entire
body
• Latency is established in dorsal root or cranial
nerve ganglia
• Antibody immunity limits viremic spread of VZV
• Cell-mediated immunity important for limiting
progression and resolving disease
20
Varicella-Zoster Virus (VZV)
shingles
chickenpox
VZV in newborn
Varicella-Zoster Virus (VZV):
treatment
• For children with chickenpox, normally supportive care
is sufficient
• Acyclovir, famciclovir and valacyclovir are used to
prevent disseminated infection in immunosuppressed
patients
• Protection for immunosuppressed patients also may
come from varicella-zoster immunoglobulin (VZIg).
This can prevent viremic spread, but is ineffective for
patients with active varicella or herpes zoster disease.
• An FDA-approved live virus vaccine is available for
VZV
21
Epstein-Barr Virus (EBV)
• First discovered as the causative agent for African Burkitt’s
lymphoma (AfBl).
• Later identified as causative agent for infectious
mononucleosis (“kissing disease”) when serum from
infected individual was found to contain antibody to AfBl.
• Tissue tropism is determined by expression of its receptor,
which is same receptor for the C3d component of the
complement system (a.k.a. CR2 or CD21). Infection is
limited to only those cell types which express this receptor.
• Encodes more than 70 proteins
• Has both semi-permissive and permissive replicative cycles
EBV Gene Expression
Semi-permissive replication
• In latently infected lymphocytes, a few unintegrated
copies are replicated every time the cell divides. Early
immediate genes are expressed, including the EBV nuclear
antigens, two latent membrane proteins (LMPs), and two
small RNA molecules (EBER-1 and EBER-2).
• The LMPs are oncogenes that stimulate growth of and
immortalize the B cell.
Permissive replication
• In epithelial cells or B cells permissive for EBV replication,
expression of ZEBRA protein activates early genes,
resulting in expression of the polymerase and DNA
replication and rest of the lytic cycle.
22
EBV Pathogenesis:
B cell transformation
• Taken up by CD21+ B lymphocytes following virus
replication in pharyngeal epithelial cells and
shedding in saliva
• Infected B cells become protected from
undergoing apoptosis; cell is transformed
• B cell transformation changes the interaction of
the cell with other immune system components
EBV Pathogenesis:
Burkitt’s lymphoma
• Tumor of the jaw and face found in children, with
evidence of EBV DNA and tumor antigens in the
tumor cells
• Tumor cells are monoclonal and show a
characteristic translocation between
chromosomes 8 and 14, which brings the c-myc
gene next to the gene for the Ig heavy chain.
• Result is elevated transcription of c-myc
• Biopsy shows large multinucleated cells
23
EBV Pathogenesis:
Burkitt’s lymphoma
EBV Pathogenesis:
Nasal Pharyngeal Cancer
• Tumor of the epithelium and upper respiratory
tract
•
Occurrences seen in south China, Alaska, Tunisia,
east Africa
• Genetic predisposition may be involved, or
possibly environmental co-factor
24
EBV Pathogenesis:
Oral Hairy Leukoplakia
• An unusual manifestation of a productive EBV
infection in HIV-infected patients with AIDS
• Characterized by a nonpainful white plaque along
the lateral tongue borders.
• May spread to contiguous sites such as the mouth
floor, tonsil, and pharynx.
EBV Pathogenesis:
Infectious mononucleosis
• Characterized by malaise, lymphadenopathy,
tonsilitis, enlarged spleen and liver, and fever,
which may persist for more than a week.
• A rash may also develop
• Resolution usually occurs in 1 to 4 weeks
• Complications can include neurological disorders,
including meningitis, encephalitis, myelitis and
Guillain-Barre syndrome.
25
EBV Diagnosis and Treatment
• Blood smears showing
atypical lymphocytes in
infectious
mononucleosis
• Serological tests are
also available for
diagnosis
• No drugs are currently
available to treat
Epstein-Barr virus, since
it lacks a thymidine
kinase
• A vaccine is under
development
Cytomegalovirus (CMV)
• Largest genome of all herpesviruses
• Only replicates in human cells
• Productive infection seen in macrophages and
fibroblasts, whereas latent infection is set up in
several cell types, including T lymphocytes and
stromal cells of the bone marrow.
• Found in a significant proportion of the population.
• Spread mediated through most secretions, including
saliva, urine, vaginal and semen.
• Maternal to fetal spread can occur during pregnancy
26
CMV and Disease:
Congenital Infection
• Most common viral cause of congenital disease.
• Up to 1/40 newborns in the United States are
infected by the virus.
• During primary infection of the mother, the virus can
spread via the placenta to the fetus.
• Abnormalities include microcephaly, rash, brain
calcification and hepatosplenomegaly.
• Can result in hearing loss or retardation
• Neonates can also receive virus through blood
transfusion, in which the titer of virus is much
higher.
CMV: Infection in the
immunocompromised host
• Pneumonia and pneumonitis, which is fatal if not
treated
• In 16-19% of patients with terminal AIDS, CMV
produces a hemorrhagic, necrotizing retinitis.
• In 10% of AIDS patients, CMV colitis or esophagitis
may develop
27
CMV: Diagnosis
• Most infections are asymptomatic and are
undetected
• Hallmark of infection is the cytomegalic cell, which
is an enlarged cell that contains a dense, central
“owl’s eye” basophilic intranuclear inclusion body
• Viral antigens can be detected using
immunofluorescent antibodies, ELISA, or PCR
CMV: Antiviral Therapy
• Ganciclovir, valganciclovir, cidofovir and foscarnet
have all been approved by the FDA for the treatment
of specific diseases resulting from CMV infection in
immunosuppressed patients
• Progression of CMV retinitis may be delayed in the
short term by intravenous ganciclovir or foscarnet.
Both are equally effective; however, foscarnet is not
as well tolerated.
• Acyclovir is not effective for CMV infections
• A vaccine is currently under development
28
HHV-6 and HHV-7
• Human herpesvirus 6 (roseola) has two variants, 6A and 6B.
• Is found worldwide and in the saliva of >90% of adults.
• Almost all children are infected by the age of two, and the
infection is life-long.
• Replicates in T and B cells
• HHV-6B causes exanthem subitum, otherwise known as
roseola infantum.
• Symptoms include fever and sometimes upper respiratory
tract infection and lymphadenopathy.
• 14 day incubation period.
• After fever subsides, a macropapular rash appears on trunk
and neck that lasts a few days.
• Human herpesvirus 7 is similar to HHV-6 and may be
responsible for some cases of exanthem subitum.
• HHV-7 binds to CD4 antigen and replicates in CD4+ T cells.
HHV-6 and HHV-7, Clinical
Manifestations
Exanthem Subitum; Roseola Infantum
29
HHV-8 (Kaposi’s Sarcomaassociated herpesvirus, or KSHV)
• Initially found in biopsy specimens of Kaposi’s sarcoma in
AIDS patients
• Like EBV, B cells are primary target, but also infects other
cell types
• HHV-8 is found in ~10% immunocompetent people in
peripheral blood lymphocytes
• Encodes several proteins with homology to human proteins
that promote growth and prevent apoptosis of infected cell
and surrounding cells.
• Characteristic opportunistic infection associated with AIDS.
Oral KSHV Clinical Manifestations
• Over 50% of AIDS patients with skin KS also have oral KS,
while 10-20% of AIDS patients have only oral KS
• Oral KS typically found on the hard and soft palates, but also
can develop on the gingiva, the anterior palate, the tongue
and the buccal mucosa
• Characterized by one or more generally flat areas, with a
reddish brown or deep purple discoloration
• A hyperplastic, or nodular, variety of KS can also be seen,
mostly on the gingiva or tongue. Hyperplastic KS will
frequently bleed.
• As disease progresses, and color can change to darker
reddish brown, even violet
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KSHV Clinical Manifestations
A. Flat Kaposi's sarcomas involving the hard and soft palates. B. Nodular
gingival Kaposi's sarcoma (arrows). C. Multiple skin Kaposi's sarcomas
in a patient with advanced AIDS.
Treatment of KSHV Oral Lesions
• Large intraoral lesions of KS can be treated with
systemic chemotherapeutic single-agents such as
vinblastine and vincristine.
• Radiation therapy is also used in large lesions
(after prior use of chlorhexidine gluconate rinse to
diminish severity of glossitis and mucositis that
are side effects of radiation)
• Small intraoral lesions can be treated with surgical
and laser excision. Nonsurgical treatment is also
effective, such as intralesional injections of
vinblastine sulfate.
31
Herpesvirus simiae (B virus)
• Indigenous to Old World monkeys, such as
macaques.
• Transmitted to humans via monkey bites or saliva,
or infected cell tissues
• 75% of human cases result in death
• Most survivors have serious neurologic damage.
• Both acyclovir and ganciclovir are recommended
for therapy, but efficacy is unknown (some
evidence for efficacy in the literature).
The take home
message:
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