08-25-2021-1108 - poxviridae smallpox varvars x bearbear (Where Petersmith Smith Petersen Covered SIV, became criminals etc. = USA America NAC)
Poxviridae
Poxviruses (see Glossary) have adopted a cunning strategy by forming their own interferon-receiving molecules which are released from the infected cell.
Poxviruses have been isolated from birds, insects, reptiles, marsupials, and mammals. The best known is variola virus (VARV), the cause of smallpox, an extinct disease that claimed millions of victims and influenced human history. All poxviruses have complex, enveloped virions that are large enough to be visible by the light microscope and contain double-stranded DNA (dsDNA) genomes with terminal hairpins linking the two DNA strands into a single polynucleotide chain. Poxvirus genes are transcribed by the virus-encoded RNA polymerase and associated transcriptional enzymes, which are packaged into the virion. Virus morphogenesis and entry have unique features, such as the possession of a thiol-oxidoreductase system to enable disulfide bond formation and morphogenesis in the cytoplasm, and a complex of several proteins for the fusion of infecting virions with the cell membrane.
Poxviruses are the largest of all animal viruses and can be visualized under the light microscope, although the details of the virion structure remain obscure. Using negative-staining electron microscopy and/or cryoelectron microscopy, parapoxvirus virions appear ovoid with long and short axes of approximately 260 and 160 nm, respectively, whereas all other poxviruses are ‘brick’-shaped, with dimensions of 350 × 250 nm on average.
Ten poxviruses infect humans (Table 170-1).2 Except for the ‘extinct’ variola virus and molluscum contagiosum virus, the poxvirus diseases are zoonoses.
The family Poxviridae is subdivided into two subfamilies: Chordopoxvirinae (poxviruses of vertebrates) and Entomopoxvirinae(poxviruses of insects). The subfamily Chordopoxvirinae is further subdivided into ten genera that include viruses that cause disease in domestic or laboratory animals (Table 7.1). A considerable and growing number of poxviruses await precise taxonomic assignment and are currently “unclassified.”
The family Poxviridae is divided into two subfamilies: Chordopoxvirinae(poxviruses of vertebrates) and Entomopoxvirinae (poxviruses of insects). The subfamily Chordopoxvirinae is divided further into nine genera, four of which (Orthipoxvirus, Parapoxvirus, Molluscipoxvirus, and Yatapoxvirus) contain viruses that cause human infections. Smallpox and molluscum contagiosum are specifically human diseases; the other two are zoonoses. The genus Leporipoxvirusincludes myxoma virus, which causes the fatal disease myxomatosis in European rabbits and was used successfully to control rabbit plagues. There are other poxviruses that have not yet been classified (Table 16.1).
Table 7.1. Poxviruses: Host Range and Geographic Distribution of Poxviruses in the Subfamily Chordopoxvirinae Subfamily Chordopoxvirinae
Genus
Virus
Major Hosts
Host Range
Geographic Distribution
Orthopoxvirus
Variola (smallpox) virus
Humans
Narrow
Eradicated globally
Vaccinia virus
Numerous: humans, cattle, buffalo, swine, rabbits
Broad
Worldwide
Cowpox virus
Numerous: rodents, domestic cats and large felids, cattle, humans, elephants, rhinoceros, okapi, mongoose, alpaca
Broad
Europe, Asia
Camelpox virus
Camels
Narrow
Asia, Africa
Ectromelia virus
Mice, voles
Narrow
Europe
Monkeypox virus
Numerous: squirrels, monkeys, anteaters, great apes, humans
Broad
Western and central Africa
Uasin Gishu disease virus
Horses
?
Eastern Africa
Tatera poxvirus
Gerbils (Tatera kempi)
?
Western Africa
Raccoon poxvirus
Raccoons
Broad
North America
Volepox virus
Voles (Microtus californicus)
?
California
Skunkpox virus
Skunks (Mephitis mephitis)
?
North America
Capripoxvirus
Sheeppox virus
Sheep, goats
Narrow
Africa, Asia
Goatpox virus
Goats, sheep
Narrow
Africa, Asia
Cervidpoxvirus
Lumpy skin disease virus
Cattle, Cape buffalo
Narrow
Africa
Deerpox virus
Deer including reindeer, gazelle
Broad
North America
Suipoxvirus
Swinepox virus
Swine
Narrow
Worldwide
Leporipoxvirus
Myxoma virus, rabbit fibroma virus
Rabbits (Oryctolagus and Sylvilagus spp.)
Narrow
Americas, Europe, Australia
Hare fibroma virus
European hare (Lepus europaeus)
Narrow
Europe
Squirrel fibroma virus
Eastern gray squirrel (Sciurus carolinensis),
Narrow
North America
Molluscipoxvirus
Molluscum contagiosum virus
Humans, nonhuman primates, birds, kangaroos, dogs and equids
Chickens, turkeys, and many other bird species from different orders
Narrow
Worldwide
Crocodylidpoxvirus
Crocodilepox virus
Crocodiles
Narrow
Africa
Parapoxvirus
Orf virus
Sheep, goats, humans (related viruses of camels and chamois)
Broad
Worldwide
Pseudocowpox virus
Cattle, humans
Narrow
Worldwide
Bovine papular stomatitis virus
Cattle, humans
Narrow
Worldwide
Ausdyk virus
Camels
Narrow
Africa, Asia
Sealpox virus
Seals, humans
Narrow
Worldwide
Parapoxvirus of red deer
Red deer
Narrow
New Zealand
Currently unclassified
Carp edema virus
Common and koi carp (Cyprinus carpio)
Narrow
Japan, Europe
Salmonid gill poxvirus
Atlantic salmon (Salmo salar)
Narrow
Norway
Squirrel Poxvirus
Red and gray squirrels
Narrow
Europe and North America
Based on phylogenetic reconstructions, a new virus order, Megavirales, has been recently proposed that would include the Poxviridae, the Asfarviridae, and other families of large DNA viruses, including giant viruses that infect protozoa (see Chapter 8: Asfarviridae and Iridoviridae, Fig. 8.1). Most of these viruses typically replicate in so-called “virus factories” in the cytoplasm of infected cells.
Smallpox (variola major) is categorized as a category A critical biological agent by the CDC because of its transmissibility, high morbidity and mortality, ability to cause panic in afflicted populations, and the extraordinary public health measures that would be required to contain an epidemic.14 Of particular concern with smallpox is evidence that it can be transmitted person-to-person via airborne droplet nuclei. This has been seen among some smallpoxpatients who have prominent respiratory symptoms.15
Smallpox, so named to differentiate it from great-pox (syphilis), was described by Edward Jenner as “the most dreadful scourge of the human species.”
The origin of VARV remains unknown, but the dubious accolade probably goes to Egypt or India. Unmistakable descriptions of smallpox were documented in fourth-century China, seventh-century India, and tenth-century Mediterranean and southwestern Asia. Moreover, Egyptian mummies buried over 3000 years ago have skin lesions that are consistent with smallpox. Before the fifteenth century, smallpox was generally confined to the Eurasian landmass. However, European colonists introduced smallpox to the Americas, central and southern Africa, and Australia between the fifteenth and eighteenth centuries with devastating consequences, as indigenous populations were decimated with case–fatality rates approaching 90%.
Molluscum contagiosum is a common infection worldwide. Incidence is highest among children younger than 5 years and those with atopic dermatitis.109 Transmission results from direct contact or through fomites such as towels. Molluscum contagiosum can be spread by sexual contact, with resulting lesions on the genitalia, inner thighs, and abdomen. Autoinoculation is common, particularly in individuals with conditions that compromise the epidermal barrier. Autoinoculation is thought to be the most common cause of lesions on the genitalia of infants and young children. However, the possibility of sexual abuse should be considered.110 Vertical transmission also has been reported.111
The incubation period varies from 2 weeks to 6 months. Molluscum contagiosum has been associated with outbreaks,112 but it usually occurs sporadically.
The poxvirus that causes MC is a double-stranded DNA virus that replicates in the cytoplasm of host epithelial cells (see Chapter 202, Poxviridae). The disease is acquired through direct contact with an infected person or from fomites and is spread by autoinoculation.
These eosinophilicviral inclusion bodies(Henderson–Patterson or molluscum bodies) become more prominent as infected keratinocytes move upward from the basal layer to the stratum corneum. This central plug of material, which is composed of virus-laden cells, can be shelled out from a lesion and examined under the microscope with 10% potassium hydroxide or with Wright or Giemsa stain. The rounded, cup-shaped mass of homogeneous cells, often with identifiable lobules, is diagnostic.
Course and Complications
Spontaneous remission often occurs within 6 to 9 months, although lesions have been known to persist for many years, and more lesions may develop by autoinoculation. Individual lesions can become secondarily inflamed and may resemble furuncles. Involvement of the eyelids is uncommon but may result in chronic conjunctivitis. The development of hundreds of lesions with little tendency for involution should alert the clinician to consider immunocompromise. Molluscum contagiosum is one of the most common cutaneous findings in acquired immune deficiency syndrome (AIDS) and AIDS-related complex, infecting 9% of these individuals. In the patient with AIDS, molluscum contagiosum is often recalcitrant to treatment and causes significant morbidity and disfigurement.
Pathogenesis
Although it is difficult to produce lesions after experimental inoculation, molluscum contagiosum is certainly contagious. Intimate physical contact, such as occurs in Turkish baths, wrestling, and sexual intercourse, has resulted in transmission of the disease.
The molluscum contagiosum virus replicates in the cytoplasm of the keratinocyte, with resulting large intracytoplasmic inclusion bodies (molluscum bodies) and proliferation of the epidermis. The center of the papule ultimately disintegrates, forming a crater and releasing molluscum bodies.
Spontaneous involution results from a host immune response that is presumed to be cell mediated. The stimulus that provokes this response after many months of inactivity is unknown, as with warts.
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