POXVIRIDAE &

HERPESVIRIDAE Irvan Maulana

PRETEST
 1. Which group of genomic type the
herpesviridae and poxviridae belong?
2. Mention the three herpesviridae
subfamilies!
 A

3. Identify the structure!

 4. What is the viral enzyme that can
phosphorylated the antiviral drugs used
against Herpesviruses?
5. what is the etiology of this disease?
What factor that can lead to this
condition?
6. A 23-year-old college student develops
malaise, fatigue, fever, swollen glands,
and pharyngitis. After empirical
treatment with ampicillin for a sore
throat, a rash appears. Heterophile
antibody and atypical lymphocytes are
detected from blood. What is the likely
etiology?
7. What is the most prevalent viral
cause of congenital disease?
8. This is (A)... And the most critical
function of this virus is (B)...
9. What is the name of the diseases
cause by HHV6 ?
10. Where is the hsv typical latency site?
HERPESVIRIDAE
Classification
 Group I (dsDNA)
 Order : Herpesvirales
 Family : Herpesviridae
 Subfamily :
Structure
 The herpesviruses are large, enveloped
viruses that contain double-stranded DNA.
 The virion is approximately 150 nm in
diameter
 The DNA core is surrounded by an
icosadeltahedral capsid containing 162
capsomeres.
 This capsid is enclosed by a glycoprotein-
containing envelope.
Replication
Herpesvirus Disease
Herpes Simplex Virus
 HSV was the first human herpesvirus to be
recognized
 There are two distinct HSV, types 1 and 2 (HSV-1
and HSV-2)
 The two viruses cross-react serologically, but
some unique proteins exist for each type.
 The virus is released by exocytosis or cell lysis.
Virus can also spread between cells through
intracellular bridges, which allows the virus to
escape antibody detection. Virus-induced
syncytia formation also spreads the infection.
 HSV can cause lytic infections of most cells
and latent infection of neurons.
 Characteristic histopathologic changes :
ballooning of infected cells, production of
Cowdry type A intranuclear inclusion bodies,
margination of chromatin, and formation of
multinucleated giant cells.
 Cytolysis are caused by : inhibition of cellular
macromolecular synthesis, the degradation of
host cell DNA, membrane permeation,
cytoskeletal disruption, and senescence of
the cell
HSV : Pathophysiology
 Oh hi there!
 You are not suppose to se this ;)
HSV - Treatment
 Most antiherpes drugs are nucleoside analogs
that are activated by the viral thymidine
kinase and inhibit the viral DNA polymerase,
an enzyme essential for viral replication and
the best antiviral drug target.
Varicella-Zoster Virus
 VZV causes chickenpox (varicella) and, upon
recurrence, causes herpes zoster, or shingles.
 The virus becomes latent in the dorsal root or
cranial nerve ganglia after the primary
infection.
 The disease is spread principally by the
respiratory route but may also be spread
through contact with skin vesicles.
VZV - Clinical Syndromes
 Varicella (chickenpox) is one of the five classic
childhood exanthems (along with rubella,
roseola, fifth disease, and measles).
 it is usually a mild disease of childhood and is
normally symptomatic, although asymptomatic
infection can occur
 Primary infection is usually more severe in adults
than in children. Interstitial pneumonia may
occur in 20% to 30% of adult patients and may be
fatal. The pneumonia results from inflammatory
reactions at this primary site of infection.
Cont.
 Varicella characteristics include fever and a
maculopapular rash
◦ spreads across the entire body but is more prevalent on
the trunk and head than on the extremities.
◦ The lesions itch and cause scratching, which may lead to
bacterial superinfection and scarring.
 In Herpes zoster, Severe pain in the area
innervated by the nerve usually precedes the
appearance of the chickenpox-like lesions.
◦ The rash is limited to a dermatome and resembles
varicella
◦ The pain could become chronic called postherpetic
neuralgia
VZV - Laboratory Diagnosis
 Direct fluorescent antibody to membrane antigen
(FAMA) test
 PCR and genome detection
 Serologic tests that detect antibodies to VZV are
used to screen populations for immunity to VZV.
(using immunofluorescence and ELISA)

Isolation of VZV is not routinely done because

the virus is labile during transport to the laboratory
and replicates poorly in vitro.
VZV - Treatment
 ACV, famciclovir, and valacyclovir have been
approved for the treatment of VZV infections.
 There is no good treatment, but analgesics and
other painkillers, topical anesthetics, or capsaicin
cream may provide some relief from the
postherpetic neuralgia that follows zoster.
 Immunosuppressed patients susceptible to
severe disease may be protected from serious
disease through the administration of VZIG.
 There is a vaccine for vzv, A live attenuated
vaccine (OKA strain)
Cytomegalovirus
 It is the most common viral cause of congenital
defects.
 Although usually causing mild or asymptomatic
disease in children and adults, CMV is particularly
important as an opportunistic pathogen in
immunocompromised patients.
 CMV infections can manifest as cytomegalic
inclusion disease, whose name derives from the
propensity for massive enlargement of CMV-
infected cells with intranuclear inclusion bodies.
CMV - Pathology
CMV - Treatment
 Antiviral drug : Ganciclovir , valganciclovir
(valyl ester of ganciclovir), cidofovir, and
foscarnet
 CMV spreads mainly by the sexual, tissue
transplantation, and transfusion routes, and
spread by these means is preventable.
 Both live and recombinant CMV vaccines are
under development.
Epstein-Barr Virus
 EBV is the B-lymphocyte parasite, and the
diseases it causes reflect this association.
 EBV is a member of the subfamily
Gammaherpesvirinae, and a tissue tropism
defined by the limited cellular expression of
its receptor.
 When human B lymphocytes are infected with
EBV, continuous cell lines can be established,
indicating that cells have been immortalized
by the virus
EBV – Pathophysiology & Immunity
EBV infection has the following three
potential outcomes:
1. EBV can replicate in B cells or epithelial cells
permissive for EBV replication and produce virus.
2. EBV can cause latent infection of memory B cells
in the presence of competent T cells.
3. EBV can stimulate and immortalize B cells.
 EBV – Clinical syndrome
 Heterophile Antibody–Positive Infectious
Mononucleosis, with triad classic syndrome:
◦ lymphadenopathy (swollen glands)
◦ splenomegaly (large spleen)
◦ exudative pharyngitis
 Epstein-Barr Virus–Induced Lymphoproliferative
Diseases
 Hairy Oral Leukoplakia
 Chronic tiredness and may also have low-grade
fever, headaches, and a sore throat.
EBV – Treatment
 No effective treatment or vaccine is available
for EBV disease
 Infection elicits lifelong immunity. Therefore,
the best means of preventing infectious
mononucleosis (for now) is exposure to the
virus early in life because the disease is more
benign in children.
 Adoptive transfer of EBV-reactive T cells
shows promise as a treatment for EBV-related
lymphoproliferative disease.
Human Herpesviruses 6 and 7
 The two variants of HHV-6, HHV-6A and
HHV-6B, and HHV-7, are members of the
genus Roseolovirus of the subfamily
Betaherpesvirinae.
 Exanthem subitum, or roseola infatum, is
caused by either HHV-6B or HHV-7
 HHV-6 primarily infects lymphocytes,
especially CD4 T cells. HHV-6 establishes a
latent infection in T cells and monocytes but
may replicate on activation of the cells.
Cont.
 It is characterized by the rapid onset of high
fever of a few days’ duration, which is
followed by a rash on the trunk and face, and
then it spreads and lasts only 24 to 48 hours.
 The disease is effectively controlled and
resolved by cell-mediated immunity, but the
virus establishes a lifelong latent infection of
T cel
Human Herpes Virus 8
 A new herpesvirus, designated HHV-8 and also
called KSHV (kaposi sarcoma herpes virus)
 KSHV is lymphotropic and is more closely related to
EBV
 KSHV is the cause of Kaposi sarcomas, vascular
tumors of mixed cellular composition
 Viral DNA can be detected in patient specimens
using PCR assays, Serologic assays are available to
measure persistent antibody to KSHV using indirect
immunofluorescence, Western blot, and enzyme-
linked immunosorbent assay formats
Cont.
 Foscarnet, famciclovir, ganciclovir, and
cidofovir have activity against KSHV
replication.
POXVIRIDAE
Classification
 Group I (dsDNA)
 Order : Megavirales
 Family : Poxviridae
Structure
 Their structure is complex and conforms to
neither icosahedral nor helical symmetry
 have a linear, double-stranded DNA genome
with fused ends
 The external surface of particles contains
ridges
 An outer lipoprotein membrane, or envelope,
encloses a core and two structures of
unknown function called lateral bodies
 Replication

FIGURE 44-2 Replication of

vaccinia virus. The core is released
into the cytoplasm, where virion
enzymes initiate transcription of
early genes. A viral-encoded
“uncoatase” enzyme then causes
the release of DNA. Viral
polymerase replicates the genome,
and late transcription occurs. DNA
and protein are assembled into
cores with the core membrane. An
outer membrane shrouds the core
containing the lateral bodies and
the enzymes required for
infectivity. The virion is
exocytosed or is released by cell
lysis.
 Smallpox (Variola)and molluscum
contagiosum (molluscipoxvirus) are strictly
human viruses.
 Smallpox is transmitted by aerosols and by
contact with lesion material or by a fomite.
 Molluscum contagiosum is spread by direct
contact or by fomites.
 Other poxvirus that natural host are
vertebrate other than human infecting human
only through accidental or occupational
exposure
 Smallpox
◦ The two variants of smallpox were variola major,
and variola minor
◦ Symptom include high fever, fatigue, severe
headache, backache, and malaise, followed by the
vesicular rash in the mouth and soon after on the
body.
◦ Vomiting, diarrhea, and excessive bleeding would
quickly follow
 Vaccinia and Vaccine-Related Disease
◦ Happen in person with immunocompromised or
have allergic reaction to the vaccine component (ex:
Vaccinia necrosum, Eczema vaccinatum)
 Orf, Cowpox, and Monkeypox
◦ single nodular lesion on the point of contact, such
as the fingers, hand, or forearm, and is hemorrhagic
(cowpox) or granulomatous (orf or pseudocowpox)
 Molluscum Contagiosum
◦ begin as papules and then become pearl-like
umbilicated nodules that are 2 to 10 mm in
diameter and have a central caseous plug that can
be squeezed out.
 Treatment of smallpox is primarily
supportive.
 Vaccinia immune globulin has not shown a
survival benefit for established disease.
 Methisazone is effective as prophylaxis but is
not useful in treatment of established
disease.
 Cidofovir has been used to treat molluscum
contagiosum and orf virus infections.
POSTEST
1. Mention 2 virus from poxviridae that
have human as its natural host!
2. what is the etiology of this disease?
3. What is the cytopathology effect of
betaherpesvirinae infection?
4. What are the transmission route for
HSV1 & HSV2 respectively?
5. Mention atleast two posible outcome
that could happen after EBV infection!
 6. What are the antiviral choice for CMV
infected patient with immunodeficiency
disorder? Mention atleast two

*jangan keseringan nogel

 7. What is the name of the
cytopathologic effect in the picture
above?
8. Mention the virus caused this disease
and what is the other name of the virus?
 9. What are three manifest / triad
classical symptoms from infection EBV?
10. What the name of disease from
question number 9? What the name
atypical cell B from that infection?