Poxviruses are a family of large, complex enveloped viruses that contain double-stranded DNA. They include viruses that infect humans and other vertebrates. Smallpox and molluscum contagiosum are human poxviruses, while viruses like vaccinia, cowpox and monkeypox can infect humans incidentally from animal hosts. Poxviruses replicate in the cytoplasm and have complex virion structures. Important human poxviruses include variola (smallpox virus), which was eradicated in the 1970s through vaccination, and molluscum contagiosum, which causes a generally mild skin infection.
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
Envelope
Lateral
bodies
3. Classification
Family Poxviridae
Subfamilies
Genera
Members
Chordopoxvirinae
Orthopoxvirus
Variola, vaccinia, cowpox, monkeypox, camelpox
(vertebrates)
Parapoxvirus
Sealpox, parapox of deer, pseudocowpox
Avipoxvirus
Canarypox, fowlpox, pigeonpox, turkeypox, penguinpox
Capripoxvirus
Goatpox, sheeppox
Leporipoxvirus
Hare fibroma, myoma, rabbit fibroma, squirrel fibroma
Suipoxvirus
Swinepox
Molluscipoxvirus
Molluscum contagium
Yatapoxvirus
Tanapox, Yaba monkey tumor
Entomopoxvirinae
Capripoxvirus 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. Pathogenesis and Immunity
After being inhaled, smallpox virus replicates in
the upper respiratory tract.
Dissemination occurs via lymphatic and cellassociated 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.
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
Smallpox
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)
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
15. VACCINIA
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
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.
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
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.