Poxviruses are brick or oval-shaped viruses with large double-stranded DNA genomes. Poxviruses exist throughout the world and cause disease in humans and many other types of animals. Poxvirus infections typically result in the formation of lesions, skin nodules, or disseminated rash.

1. Poxviruses
Smallpox has been
eradicated. The remaining
poxviruses pathogenic for
humans cause skin lesions
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2. Introduction
• The last endemic case of smallpox occurred in 1977
• Total eradication was confirmed in 1980, and the official account of the disease and its eradication has
appeared
• Consequently, smallpox is not discussed below. However, its importance should not be forgotten. It helped to
shape history
• It made history by being the first disease to be controlled by immunization and the first to be eradicated
• The remaining poxvirus infections of humans are relatively insignificant

3. Introduction
Virus and its reservoir Disease
Molluscum Virus in humans Skin nodules, Multiple and long lasting
Milker’s nodes virus in cattle Skin lesions similar to cowpox
Cowpox virus in wild rodents Localized hemorrhagic ulcer, painful
Monkey pox virus may be in
squirrels
Resemble human smallpox
Smallpox Virus in humans Generalized infection with pustular rash
Vaccinia virus (no generalized host) Rare complication of vaccination
Poxviruses pathogenic to humans

4. Clinical manifestations
• Poxvirus infections are characterized by the production of skin lesions
• With most poxviruses there is typically just a primary lesion, but generalized lesions develop with human
monkeypox and molluscum
• In human cowpox and parapox infections the lesion develops at the site of inoculation (usually the hand), and
infection may be spread to other sites such as the face and/or genitals by scratching.
• Parapox and molluscum infections are relatively painless and cause very little disturbance
• Human cowpox is very painful, particularly in young children, usually causes pyrexia and marked
lymphadenopathy; patients often require hospitalization
• Rare encephalitic complications of cowpox have been reported
• erythema multiforme is a complication of parapox infections

5. Clinical manifestations
• Infection in immunocompromised or eczematous individuals is more severe and usually results in generalized
illness, and in cowpox has caused deaths.
• Although human monkeypox is rare and geographically localized, it is a serious generalized infection, which
clinically resembles mild smallpox

6. Clinical manifestations
Erythema multiforme is a
hypersensitivity reaction usually
triggered by infections
Parapox virus pus filled nodules
formed on finger
Milker’s Nodule

7. Structure
• Poxvirus virions are large and brick shaped
• Orthopoxviruses are approximately 240 nm by 300 nm, with short surface tubules 10 nm wide
• Parapoxviruses are narrower (160 nm) and have one long tubule that winds around the virion
Poxvirus

8. Structure
Vaccinia Virus
Perspective: Discovery of antivirals against smallpox, September 2004 Proceedings of the National Academy of Sciences 101(31):11178-92, SourcePubMed

9. Multiplication
• Poxvirus replication takes place in cytoplasmic inclusions
• Infecting virions are partly uncoated by cellular enzymes and then fully uncoated by viral enzymes released
from the virion core
• The viral DNA is not infectious and other core enzymes (including a DNA-dependent RNA polymerase) play
essential roles in the replication cycle
• The replication cycle can be divided into functions controlled by early (prereplicative) gene products and those
controlled by late (postreplicative) gene products
• Most virions (80 to 90 percent) remain within cells

10. Recombinant Vaccinia Virus Vaccines

11. Recombinant Vaccinia Virus Vaccines
• Knowledge of the molecular biology of poxvirus replication has led to the development of recombinant vaccinia
virus strains that code for the products of foreign genes inserted into the vaccinia virus genome (previous slide)
• Such recombinants are infectious and are being widely used to study gene expression, as candidate vaccines
(e.g., against rabies), and for the production of biopharmaceuticals such as factor VIII known as anti-hemophilic
factor (AHF)
• An extension of these studies has led to the development of canarypox recombinants which express foreign
genes in mammals without causing productive infection

12. Pathogenesis
• The pathogenesis of localized poxvirus infections is simple
• Virus invades through broken skin, replicates at the site of inoculation, and causes dermal hyperplasia and
leukocyte infiltration
• With cowpox, and parapox, there is limited lymphatic spread; this causes lymphadenopathy and elicits an
immune response
• The lesion of molluscum is a connective tissue capsule, and the dermis is not usually broken
• Some poxviruses express an epidermal growth factor and host range genes which play a role in pathogenesis
and distortion of dermis

13. Pathogenesis
• Human monkeypox is usually acquired via the respiratory tract, and during a 12-day incubation period viremia
distributes infection to internal organs, which are damaged by virus infection
• Spread to the skin initiates the clinical phase, and the lesions progress through the classic stages of macule to
papule to vesicle to pustule to crust
• Lymphadenopathy, usually involving the cervical and inguinal areas, is often marked
• With the exception of molluscum, which is a specifically human disease, human poxvirus infections are acquired
from animal reservoirs
• Monkeypox is restricted to West Africa, and squirrels are more important as reservoir hosts than monkeys
• Cowpox virus is restricted to Europe and western parts of the former USSR
• Bovine cowpox is rare, and the domestic cat is the most commonly reported host.

14. Diagnosis
• In many cases, the nature of the lesions and a careful history that establishes contact with an infected reservoir
animal or another infected person will permit a satisfactory diagnosis
• Difficulties may arise if no such contact is established - most common with human cowpox, since most cases are
not traced to a particular source
• Electron microscopy of vesicle or scab material is an effective means of rapid diagnosis; poxviruses and
herpesviruses are readily distinguished, and the characteristic morphology of parapoxviruses can be recognized
• Immunofluorescence of infected cell cultures will differentiate morphologically similar poxviruses from different
genera
• knowledge of host and geographic range will help to confirm a presumptive diagnosis
• Precise identification by antibody detection is compromised by close antigenic relationships within genera

15. Edward Jenner
In 1796, English physician Edward Jenner infected
a young boy with cowpox. Later, when he injected
the child with the deadly smallpox virus, he did
not get sick. And thus, the first vaccine was born,
saving millions of lives and immortalizing cows in
public health. (The word vaccine is derived from
the Latin word vacca for “cow.”)

16. What is Smallpox Virus
Smallpox is caused by the variola virus, a DNA virus of the genus Orthopoxvirus. Humans are the only
known reservoir for this virus. It is transmitted from person to person, and natural infection occurs by
inhalation of respiratory droplets or contact with infected material on mucous membranes.
After a 10 to 14 day incubation period, the infected person develops severe symptoms with fever,
malaise and headache.3 A maculopapular rash then develops with involvement of the face, mucous
membranes, trunk and extremities. The lesions become pustular and deep over the subsequent 1 to
2 days, with scab formation by day 10. Patients are most infectious during the first week of the rash
when viral shedding is greatest from ulcerated lesions in the oral mucosa. The overall mortality rate is
about 30%, with most deaths occurring during the second week of illness.

17. How did Edward Jenner find the Vaccine for Smallpox?
Jenner had heard that milkmaids were protected from the disease smallpox after having
suffered cowpox which was prevalent then. He thus concluded that cowpox could help stop
the spread of smallpox.
He used matter from the lesions of a maid suffering from cowpox and inoculated an 8 yr old
boy. The boy developed mild fever and some discomfort. Nine days later he felt cold, lost
appetite but improved and became much better the following day. Two months later Jenner
inoculated the boy again from a fresh smallpox lesion but the boy did not develop the
disease.

18. How did Edward Jenner find the Vaccine for Smallpox?
• He communicated his observations to the Royal Society which rejected them. He then
published a small booklet privately and called his new procedure vaccination.
• Jenner’s vaccination received public acknowledgement in 1802 with the British Parliament
granting him sums of money.
• He received many honours but was subjected to ridicule as well. This did not deter him
from working with his vaccination programme.
• His was the first scientific attempt using vaccination to control an infectious disease.

19. First person to Vaccinate against Smallpox
• Benjamin Jesty is being considered as the first
person to vaccinate against smallpox.
• Jenner they say was not the first to vaccinate but
gave the vaccination its scientific recognition.
• Jesty to protect his family from smallpox used
material from the udders of cattle that he knew
had cowpox and transferred the material into his
wife’s arm.

20. The World Health Assembly declared that smallpox had been
eradicated from the earth in 1980
it stands as one of the greatest accomplishments of the 20th
century, if not one of the greatest human accomplishments of
all time.