4.

Poxviruses: Smallpox and Cowpox

Suzan Matar
PhD in Medical Microbiology and Immunology
Smallpox

Humans are the

only natural
hosts
 The early vaccines
were derived from
cowpox
(vacca=cow)

Later, other
vaccines using
strains of poxvirus
(vaccinia) were
used.
 Poxviruses

Smallpox is considered a category A agent by

the Centers for Disease Control and Prevention
(CDC), with anthrax, plague, botulism, tularemia
because of their great potential as bioterrorism-
biowarfare agents.
 Properties of Poxviruses
Structure and composition
Enveloped
Largest viruses
Linear dsDNA
Brick shaped
core (contains nucleic acid)
Lateral bodies (unknown function)

More than 100 polypeptides

Many target the immune response
Replicate in cytoplasm (too big to get into nucleus)
Tend to be highly species-specific
Some are being explored as gene therapy vectors
 Structure and Replication

They replicate only in the cytoplasm and

transport into the cell transcriptases,
capping and methylating enzymes and
poly(A) polymerase.

Viral DNA then replicates in electron-dense

cytoplasmic inclusions (Guarnieri's inclusion
bodies), referred to as factories.
Poxiviridiae
 Variolation

An early approach to immunization, involved the

inoculation of susceptible people with the virulent
smallpox pus. It was first performed in the Far East
and later in England.

Variolation was associated with a fatality rate of

approximately 1%, a better risk than that
associated with smallpox itself.

In 1796, Jenner developed and then popularized

a vaccine using the less virulent cowpox virus,
which shares antigenic determinants with
smallpox.
 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.
 Despite the severity of the disease and its
tendency to spread, several factors contributed
to its elimination.
 Properties of Natural Smallpox That Led
to Its Eradication
Viral Characteristics
Exclusive human host range (no animal reservoirs or vectors)
Single serotype (immunization protected against all
infections)

Disease Characteristics
Consistent disease presentation with visible pustules
(identification of sources of contagion allowed quarantine
and vaccination of contacts) no asympotomatic carriers
Short infectivity period (3-4 weeks)

Vaccine
Immunization with animal poxviruses protects against
smallpox . Stable, inexpensive, and easy-to-administer
vaccine . Presence of scar indicating successful
vaccination
 Pathogenesis and Immunity
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.
 Most infectious
Might be contagious
contagious
 Immune response
- An early IgM response was followed by the
appearance of IgG antibody, which persisted
for many years.

- An attack nearly always conferred lifelong

immunity, mediated by neutralizing antibody.

- Recovery from infection was, however, largely

effected by cell-mediated responses.
 EM is the most important technique for
diagnosing all poxvirus infections and
units able to rapidly diagnose smallpox
have been set up again to counter
bioterrorism or natural emergence of
monkey pox.