Poxviruses

The variola virus, which belongs to the genus Orthopoxvirus and is the causative agent in smallpox, was declared eradicated in 1980 after a WHO vaccination campaign. The vaccinia virus, used at the end of the 18^th century by E. Jenner in England as a vaccine virus to protect against smallpox, is now used as a vector in molecular biology and as a hybrid virus with determinants from other viruses in experimental vaccines. Among the other orthopox­viruses found in animals, the monkeypox viruses are the main human patho­gens. The animal pathogens parapoxviruses (milker's nodules, orf) are occa­sionally transmitted to humans, in whom they cause harmless exanthems.

The molloscum contagiosum virus affects only humans and causes benign tumors.

Diagnosis. Orthopoxviruses and parapoxviruses: electron microscopy. Molloscum contagiosum: histology.

Pathogens. The viruses of the pox group are the largest viruses of all. At 230 x 350 nm they are just within the resolution range of light microscopes. They have a complex structure (Fig. 1) and are the only DNA viruses that replicate in a defined area within the host-cell cytoplasm, a so-called “virus factory" (Fig. 2).

The diseases smallpox (variola major) and the milder form alastrim (var­iola minor) now no longer occur in the human population thanks to a world­wide vaccination program during the 1970s. The last person infected by smallpox was registered in Somalia in 1977 and eradication of the disease was formally proclaimed in 1980. Since then, populations of the virus have been preserved in two special laboratories only.

Fig. 1 Poxviruses measure 200-350 nm, putting them just within the resolution range of light microscopes (TEM).

Fig. 2 The vaccinia viruses are the dark, electron-dense inclu­sions readily visible here. They replicate in a discrete cytoplasmic region (TEM).

Pathogenesis and clinical picture. Variola viruses are transmitted aerogenically. The mucosa of the upper respiratory tract provides the portal of entry. From there, the pathogens enter the lymphoid organs and finally penetrate to the skin, where typical eruptions form and, unlike varicella pustules, all de­velop together through the same stages (Fig. 3). The mucosae of the respira­tory and intestinal tracts are also affected. Lethality rates in cases of smallpox (variola major) were as high as 40%. In alastrim (variola minor) the level was 2 %, whereby the cause of death was often a bronchopneumonia.

The vaccinia virus is a distinct viral type of unknown origins, and not an attenuated variola virus. It was formerly used as a vaccine virus to protect against smallpox. The vaccination caused a pustular exanthem around the vaccination site, usually accompanied by fever. Encephalitis, the pathogenesis of which was never completely clarified, was a feared complication. It is as­sumed that an autoimmune reaction was the decisive factor. Other complica­tions include generalized vaccinia infection and vaccinial keratitis. Vaccinia infections and their complications disappeared for the most part when small­pox was eradicated by the WHO vaccination campaign. Vaccinia viruses are still frequently used as vectors in molecular biology laboratories. The inher­ent pathogenicity of the virus should of course be kept in mind by experimen­ters.

Infections with cowpox, orf, and milker's nodule viruses are rare and usual­ly harmless. The lesions remain localized on the skin (contact site), accom­panied by a local lymphadenitis. These are typical occupational infections (farmers, veterinarians). The molluscum contagiosum virus is unusual in that in-vitro culturing of the virus has not succeeded to date. Infections with this virus do not confer immunity. The infection causes epidermal, benign tumors (“molluscum contagiosum warts”).

Fig. 3 In contrast to the lesions in varicella infections, all smallpox pustules are at the same developmental stage.

Diagnosis. The poxviruses groups are relatively easy to recognize under an electron microscope in pustule contents, provided the pustules have not yet dried out or been superinfected with bacteria. Orthopoxviruses and para­poxviruses can be differentiated morphologically, but the viruses within each genus share the same morphology. Molluscum contagiosum is diagnosed his­tologically.

Epidemiology and prevention. Diseased humans were the sole viral reser­voir of variola and alastrim. Transmission was direct and aerogenic and, although the virus is highly resistant even when desiccated, less frequent via contaminated objects (bed linens). The vaccinia virus does not occur in nature and any human infections are now accidental (laboratory infections).

The zootropic poxviruses are transmitted solely by means of contact with infected animals. Molluscum contagiosum is transmitted by interhuman contact.