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 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.

Viral DNA into the cell cytoplasm. Viral DNA then replicates in electron-dense cytoplasmic inclusions (Guarnieri's inclusion bodies), referred to as factories Replication of vaccinia virus. 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 Spread of smallpox within the body. BOX 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.

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 BOX 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 VirusDiseaseSourceLocation VariolaSmallpox (now extinct)HumansExtinct VacciniaUsed for smallpox vaccination Laboratory product- OrfLocalized lesionZoonosis-sheep, goatsWorldwide CowpoxLocalized lesionZoonosis-rodents, cats, cows Europe PseudocowpoxMilker's noduleZoonosis-dairy cowsWorldwide MonkeypoxGeneralized diseaseZoonosis-monkeys, squirrels Africa Bovine papular stomatitis virus Localized lesionZoonosis-calves, beef cattle Worldwide TanapoxLocalized lesionRare zoonosis-monkeysAfrica YabapoxLocalized lesionRare zoonosis-monkeys, baboons Africa Molluscum contagiosumMany skin lesionsHumansWorldwide Table Diseases Associated with Poxviruses

SMALLPOX - characteristic rash is shown in Figure 54-5.Figure 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.Cidofovir

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).Figure 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 – 사마귀 성 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.