Poxviruses

1
Poxviruses
2

• Orthopoxvirus
• - Variola virus (??(??)????) - Human viruses
  variola (smallpox)
• - Cowpox virus (??????)
• - Monkeypox virus (?????????)
• - Vaccinia virus (????????)
• molluscum contagiosum (genus Molluscipoxvirus)
• Vaccinia, canary pox viruses gene delivery
  vector
• Biowarfare

3
Structure and Replication
BOX 54-1. Unique Properties of Poxviruses
Poxviruses are the largest, most complex viruses (230 x 300 nm, visible on light microscopy). Poxviruses have complex, oval to brick-shaped morphology with internal structure. Poxviruses have a linear, double-stranded DNA genome with fused ends. - 86kb (120kDa), ITR Poxviruses are DNA viruses that replicate in the cytoplasm. Virus encodes and carries all proteins necessary for mRNA synthesis. Virus also encodes proteins for functions such as DNA synthesis, nucleotide scavenging, and immune escape mechanisms. Virus is assembled in inclusion bodies (Guarnieri's bodies), where it acquires its outer membranes.
A. Structure of the vaccinia virus. Within the
virion, the core assumes the shape of a dumbbell
because of the large lateral bodies. Virions have
a double membrane the "outer membrane" assembles
around the core in the cytoplasm, and the
envelope is acquired on exit from the cell. B,
Electron micrographs of orf virus. Note its
complex structure.
4
Replication of vaccinia virus.
Viral DNA into the cell cytoplasm. Viral DNA then
replicates in electron-dense cytoplasmic
inclusions (Guarnieri's inclusion bodies),
referred to as factories
In poxviruses, unlike other viruses, the
membranes assemble around the core factories.
Approximately 10,000 viral particles are produced
per infected cell and are released on cell lysis.
5
Vaccinia virus as an expression vector for the
production of live recombinant vaccines.
6
Pathogenesis and Immunity
BOX 54-2. Disease Mechanisms of Poxvirus
Smallpox is initiated by respiratory tract infection and is spread mainly by the lymphatic system and cell-associated viremia. Molluscum contagiosum and zoonoses are transmitted by contact. Virus may cause initial stimulation of cell growth and then cell lysis. Virus encodes immune escape mechanisms. Cell-mediated immunity and humoral immunity are important for resolution. Most poxviruses share antigenic determinants allowing preparation of "safe" live vaccines from animal poxviruses.
Spread of smallpox within the body.
7
Epidemiology
- Smallpox (variola) was very contagious and, as
just noted, was spread primarily by the
respiratory route. It was also spread less
efficiently through close contact with dried
virus on clothes or other materials. Despite the
severity of the disease and its tendency to
spread, several factors contributed to its
elimination, as listed in Box 54-3.

BOX 54-3. 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)
• Vaccine
• - Immunization with animal poxviruses protects
  against smallpox
• - Stable, inexpensive, and easy-to-administer
  vaccine
• - Presence of scar indicating successful
  vaccination
• Public Health Service Successful worldwide WHO
  program combining vaccination and quarantine

8
Clinical Syndromes
Table 54-1. Diseases Associated with Poxviruses
Virus Disease Source Location
Variola Smallpox (now extinct) Humans Extinct
Vaccinia Used for smallpox vaccination Laboratory product -
Orf Localized lesion Zoonosis-sheep, goats Worldwide
Cowpox Localized lesion Zoonosis-rodents, cats, cows Europe
Pseudocowpox Milker's nodule Zoonosis-dairy cows Worldwide
Monkeypox Generalized disease Zoonosis-monkeys, squirrels Africa
Bovine papular stomatitis virus Localized lesion Zoonosis-calves, beef cattle Worldwide
Tanapox Localized lesion Rare zoonosis-monkeys Africa
Yabapox Localized lesion Rare zoonosis-monkeys, baboons Africa
Molluscum contagiosum Many skin lesions Humans Worldwide

9
SMALLPOX

• characteristic rash is shown in Figure 54-5.
• After a 5- to 17-day incubation period
• 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
  soon follow. The simultaneous outbreak of the
  vesicular rash distinguishes smallpox from the
  vesicles of varicella-zoster, which erupt in
  successive crops.

10
Diagnosis growth of the virus in embryonated
eggs or cell cultures.
Characteristic lesions (pocks) embryonated
eggs. PCR
Variolation (??) inoculation of susceptible
people with the virulent smallpox pus. -
intranasally, intradermally a fatality
rate of approximately 1 In 1796, Jenner
developed and then popularized a vaccine using
the less virulent cowpox virus, which shares
antigenic determinants with smallpox.
Antiviral drugs Cidofovir  , a nucleotide
analogue capable of inhibiting the viral DNA
polymerase, is effective and approved for
treatment of poxvirus infections.
11
VACCINIA
Vaccinia a form of cowpox,
smallpox vaccine.
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. -
fingers, hand, or forearm, and is hemorrhagic
(cowpox) or granulomatous (orf or pseudocowpox)
(Figure 54-6).
- Monkeypox virus illnesses resembling smallpox
mild version of smallpox disease, including the
pocklike rash.
12
MOLLUSCUM CONTAGIOSUM (?????, ??? ???)

• - The lesions of molluscum contagiosum differ
  significantly from pox lesions in being nodular
  to wartlike (?????, ??? ????)
• papules ? pearl-like, umbilicated nodules ?
  central caseous plug
• spread by direct contact (e.g., sexual contact,
  wrestling) or fomites (e.g., towels).
• more common in children than adults, but its
  incidence is increasing in sexually active
  individuals.

Diagnosis characteristic large, eosinophilic
cytoplasmic inclusions (molluscum bodies) in
epithelial cells ???? ??? ?? biopsy specimens
or in the expressed caseous core of a nodule

• Lesions of molluscum contagiosum disappear in 2
  to 12 months
• The nodules can be removed by curettage
  (scraping) or the application of liquid nitrogen
  or iodine solutions.