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Poxviruses_Chapter 54_.ppt

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					Poxviruses
- Orthopoxvirus
    - Variola virus (두창(마마)바이러스) - Human viruses variola (smallpox)
    - Cowpox virus (우두바이러스)
    - Monkeypox virus (원숭이폭스바이러스)
    - Vaccinia virus (백시니아바이러스)

- molluscum contagiosum (genus Molluscipoxvirus)

- Vaccinia, canary pox viruses : gene delivery vector

- Biowarfare
                        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.
                             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.
Vaccinia virus as an expression vector for the
  production of live recombinant vaccines.
                              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
Spread of smallpox within the body.         animal poxviruses.
                                       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
                                 Clinical Syndromes

                   Table 54-1. Diseases Associated with Poxviruses

Virus                     Disease                  Source                    Location
Variola                   Smallpox (now extinct)   Humans                    Extinct
Vaccinia                  Used for smallpox        Laboratory product        -
                          vaccination
Orf                       Localized lesion         Zoonosis-sheep, goats     Worldwide
Cowpox                    Localized lesion         Zoonosis-rodents, cats,   Europe
                                                   cows
Pseudocowpox              Milker's nodule          Zoonosis-dairy cows       Worldwide
Monkeypox                 Generalized disease      Zoonosis-monkeys,         Africa
                                                   squirrels
Bovine papular            Localized lesion         Zoonosis-calves, beef     Worldwide
stomatitis virus                                   cattle
Tanapox                   Localized lesion         Rare zoonosis-monkeys     Africa
Yabapox                   Localized lesion         Rare zoonosis-monkeys,    Africa
                                                   baboons
Molluscum contagiosum     Many skin lesions        Humans                    Worldwide
                                 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.
Diagnosis : growth of the virus in embryonated eggs or cell cultures.
            Characteristic lesions (pocks) embryonated eggs.
            PCR

Variolation (종두)
   : 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.
                                    VACCINIA
   Vaccinia : a form of cowpox,
                smallpox vaccine.

           ORF (영아구창바이러스), 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.
             MOLLUSCUM CONTAGIOSUM (전염물렁증, 전염성 연속종)

- The lesions of molluscum contagiosum differ significantly from pox lesions in
  being nodular to wartlike (사마귀종류, 양성의 표피종양)
- 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 – 사마
귀성 상피의 증식
 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.

				
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