Poxviruses

virology

1. Poxviruses
By: Lopez, Aileen P.
Mundo, Argelyn M.

2. Properties of Poxviruses
Structure and composition
Largest viruses
dsDNA, 130-375 kb
Brick shaped
“dumbbell” core (contains nucleic acid)
Lateral bodies (unknown function)
Enveloped
Resistant to inactivation
More than 100 polypeptides
Many target the immune response
Replicate in cytoplasm
Tend to be highly species-specific
Some are being explored as gene therapy
vectors
Core
Lateral
bodies
Envelope

3. Classification
Family Poxviridae
Subfamilies Genera Members
ChordopoxvirinaeOrthopoxvirus Variola, vaccinia, cowpox, monkeypox, camelpox
(vertebrates) Parapoxvirus Sealpox, parapox of deer, pseudocowpox
AvipoxvirusCanarypox, fowlpox, pigeonpox, turkeypox, penguinpox
Capripoxvirus Goatpox, sheeppox
LeporipoxvirusHare fibroma, myoma, rabbit fibroma, squirrel fibroma
Suipoxvirus Swinepox
Molluscipoxvirus Molluscum contagium
Yatapoxvirus Tanapox, Yaba monkey tumor
EntomopoxvirinaeCapripoxvirus A
(insects) Capripoxvirus B
Capripoxvirus C

4. Poxviruses
Include the human viruses variola (smallpox) and
molluscum contagiosum
Some viruses naturally infect animals and can cause
incidental infection in humans (zoonosis).
Many of these viruses share antigenic determinants with
smallpox, allowing the use of an animal poxvirus for a
human vaccine.

5. The largest viruses, almost visible on light microscopy
(300 nm) and are ovoid to brick shaped with a complex
morphology.

6. Replication
Attachment, penetration and uncoating
Membrane fusion
Viral core dissociates, releasing
Viral DNA
Viral enzymes
Virally-encoded RNA polymerase (prepackaged) synthesizes
early mRNA
Early proteins
DNA polymerase
Thymidine kinase
Recombinase?
Maturation
Structural proteins are synthesized
Virus synthesizes its own membranes
Some virus exits by budding, but most when the cell dies

8. After being inhaled, smallpox virus replicates in
the upper respiratory tract.
Dissemination occurs via lymphatic and cell-
associated viremic spread.
Internal and dermal tissues are inoculated after a
second viremia, causing the simultaneous eruption
of the characteristic "pocks.“
Molluscum contagiosum and the other poxviruses,
however, are acquired through direct contact with
lesions.
Pathogenesis and Immunity

10. Epidemiology
Smallpox and molluscum contagiousum are strictly
human viruses.
In contrast, the natural hosts for the other
poxviruses important to humans are vertebrates
other than humans (e.g., cow, sheep, goats).
The viruses infect humans only through accidental
or occupational exposure (zoonosis).

11. Clinical Syndromes
Smallpox
Named smallpox to discriminate it from
largepox (syphilis)
No animal reservoir
Two species
Variola major (20% fatality)
Variola minor (1-2% fatality)
Smallpox has shaped civilization
Earliest evidence: Egyptian mummies
Ramses V (1157 BC)
Introduced to the Americas by European explorers
British army used smallpox as a biological weapon
against the Pontiac Indians
About 40 million native Americans died from
European diseases, including smallpox
Native Americans have limited MHC polymorphisms
Killed 300 million people in the 20th century alone
Total fatalities probably near 1 billion

12. Control and Eradication
Vaccine
Edward Jenner observed that milkmaids rarely contracted
smallpox
All had recalled earlier cowpox infections, which were nearly
universal in milkmaids
Cowpox only causes a mild infection in humans
Jenner hypothesized that the infectious agent of cowpox protected
against smallpox
He inoculated a nephew by scarification with cowpox crusts
termed variolation
Today’s vaccine is live attenuated vaccinia virus
Vaccinia’s genome looks similar to cowpox, but it is not
identical
In the 1950s, the Soviets proposed a global eradication
program to the United Nations
Some have suggested that the Soviets had a vaccine-resistant
strain of variola, which could be used as a bioweapon
The World Health Organization (WHO) Intensified Smallpox
Eradication Programme program began in 1967
Smallpox was declared eradicated in 1980 (last case in 1977)
Only two nations are supposed to have smallpox viruses today
United States (CDC-Atlanta)
Russia (VECTOR, Moscow)
Smallpox

13. Smallpox Pathogenesis
Respiratory transmission
Incubation period 10-14 days
After day 7 or so, humans begin shedding virus
asymptomatically
Principal reason for rapid spread
Outbreaks tended to be in clusters
Allowed the ring immunization containment strategy during
the eradication program
Clinical symptoms
Fever
Malaise
Centrifugally-distributed exanthems
macules
papules
pustules

14. Clinical
progression of
smallpox

15. Vaccinia, a form of cowpox, was used for the
smallpox vaccine.
The vaccination procedure consisted of scratching
live virus into the patient's skin and then observing
for the development of vesicles and pustules.
Encephalitis and progressive infection (vaccinia
necrosum), the latter occurring occasionally in
immunocompromised patients
VACCINIA

16. ORF, COWPOX, AND MONKEYPOX
Human infection with the orf (poxvirus of sheep and
goat) or cowpox (vaccinia) virus is usually an
occupational hazard resulting from direct contact
with the lesions on the animal.
A single nodular lesion usually forms on the point of
contact, such as the fingers, hand and is
hemorrhagic or granulomatous.
Then regress in 25 to 35 days, generally without
scar formation. The lesions may be mistaken for
anthrax.
Monkeypox causes a milder version of smallpox
disease.

17. Orf

18. MOLLUSCUM CONTAGIOSUM
The lesions differ significantly from pox lesions in
being nodular to wartlike.
Begin as papules and then become pearl-like,
umbilicated nodules that have a central caseous
plug.
The incubation period for molluscum contagiosum is
2 to 8 weeks, and the disease is spread by direct
contact (e.g., sexual contact, wrestling) or fomites
(e.g., towels).

19. MOLLUSCUM CONTAGIOSUM
They are most
common on the trunk,
genitalia, and
proximal extremities
and usually occur in a
cluster of five to 20
nodules.
The disease is more
common in children
than adults, but its
incidence is
increasing in sexually
active individuals.

20. Diagnosis
Confirmed histologically by the finding of
characteristic large, eosinophilic cytoplasmic
inclusions (molluscum bodies) in epithelial cells.
These bodies can be seen in biopsy specimens

21. Epidermis is
filled with
molluscum bodies

22. Lesions of molluscum contagiosum disappear in 2 to
12 months, presumably as a result of immune
responses.
The nodules can be removed by curettage
(scraping) or the application of liquid nitrogen or
iodine solutions.

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