|Group:||Group I (dsDNA)|
Orthopoxvirus is a genus of viruses, in the family Poxviridae, in the subfamily Chordopoxvirinae. Mammals, human, vertebrates, and arthropods serve as natural hosts. There are currently ten species in this genus including the type species Vaccinia virus. Diseases associated with this genus include: variola virus: smallpox cowpox, horsepox, monkeypox: asymptomatic in human. The most famous member of the genus is Variola virus, which causes smallpox. It was eradicated using another orthopoxvirus, Vaccinia virus, as a vaccine.
Viruses in Orthopoxvirus are enveloped, with brick-shaped geometries. These viruses are about 200 nm wide and 250 nm long. Genomes are linear, around 170-250kb in length.
|Genus||Structure||Symmetry||Capsid||Genomic Arrangement||Genomic Segmentation|
Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host glycosaminoglycans (GAGs) mediates endocytosis of the virus into the host cell. Fusion with the plasma membrane to release the core into the host cytoplasm. Early phase: early genes are transcribed in the cytoplasm by viral RNA polymerase. Early expression begins at 30 minutes post-infection. Core is completely uncoated as early expression ends, viral genome is now free in the cytoplasm. Intermediate phase: Intermediate genes are expressed, triggering genomic DNA replication at approximately 100 minutes post-infection. Late phase: Late genes are expressed from 140 min to 48 hours post-infection, producing all structural proteins. Assembly of progeny virions starts in cytoplasmic viral factories, producing an spherical immature particle. This virus particle matures into brick-shaped intracellular mature virion (IMV). IMV virion can be released upon cell lysis, or can acquire a second double membrane from trans-Golgi and bud as external enveloped virion (EEV)host receptors, which mediates endocytosis. Replication follows the DNA strand displacement model. DNA-templated transcription is the method of transcription. The virus exits the host cell by microtubular outwards viral transport, and existing in occlusion bodies after cell death and remaining infectious until finding another host. Mammals, human, vertebrates, and arthropods serve as the natural host. Transmission routes are zoonosis, contact, and respiratory.
|Genus||Host Details||Tissue Tropism||Entry Details||Release Details||Replication Site||Assembly Site||Transmission|
|Orthopoxvirus||Humans; mammals||None||Glycosaminoglycans||Lysis; budding||Cytoplasm||Cytoplasm||Variola virus; Respiratory; contact; zoonosis|
Some orthopoxviruses, particularly monkeypox, cowpox and buffalopox viruses have the ability to infect non-reservoir species. Others, such as ectromelia and camelpox viruses, are very host specific. Vaccinia virus, maintained in vaccine institutes and research laboratories, has a very wide host range and has caused natural infections in cattle and Indian buffalo. Now that smallpox has been eradicated, camelpox is probably the most important Orthpoxvirus infection. Many subsistence-level nomadic communities depend on their camels in countries such as Iran, Iraq, Somalia, Kenya and Ethiopia.
Human Orthopoxvirus disease
With the eradication of smallpox, human Orthopoxvirus infections are zoonoses When investigating human infections information about the geographical spread and host range can be of great value. Monkeypox occurs naturally only in Africa, particularly Zaire. However, human cases have occurred in the US initially acquired from animals imported from Ghana, also from prairie dogs infected by contact with the imported animals. Cowpox only occurs in Europe and adjacent Russian states and despite its name occurs only rarely in cattle. The most commonly detected host is the domestic cat from which human infections are most often acquired. Cowpox virus has infected a variety of exotic animals such as elephants in European zoos, resulting in human infection.
Aerosols of concentrated virus may result in orthopoxvirus infection, especially in non-immunized individuals. Needle sticks especially with concentrated viruses or scratches from infected animals may result in local infection of the skin even in immunized individuals. Cowpox infection in Europe is an occupational hazard for veterinary workers, less so for farmworkers. The widespread cessation of smallpox vaccination should reduce the occurrence of complications it occasionally produced.
Signs and Symptoms
The initial symptoms include fever, malaise, head and body aches, and sometimes vomiting. With the exception of monkeypox, one lesion is the norm, though satellite lesions may be produced by accidental autoinoculation. Individual lesions, surrounded by inflammatory tissue, develop and progress through macules, papules, vesicles, and pustules and eventually dry crusts. They are not particularly diagnostic of Orthopoxvirus infection and may be mistaken for zoonotic Parapoxvirus infections, anthrax or Herpesvirus infections  Severe edema and erythema may affect large areas in cases of severe infection. Encephalitis (alteration of mental status and focal neurologic deficits), myelitis (upper- and lower-motor neuron dysfunction, sensory level and bowel and bladder dysfunction), or both may result from Orthopoxvirus infection. Rarely, orthopoxviruses may be detected in cerebrospinal fluid. Human monkeypox resembles mild smallpox and a survey in Zaire reported no deaths in vaccinated patients or in children >10 years old. The crude mortality in the unvaccinated was 11%, and 15% in children 0–4 years old. Human cowpox is a relatively severe localized infection. A survey of 54 cases reported three cases of generalised infection including one death. It is possible that the severity of two of these cases was increased by conditions that would have contraindicated smallpox vaccination.
Vaccinia-specific immunoglobulins may be administered to infected individuals. The only product currently available for treatment of complications of orthopox infection is vaccinia immunoglobulin (VIG), which is an isotonic sterile solution of the immunoglobulin fraction of plasma from persons vaccinated with vaccinia vaccine. It is effective for treatment of eczema vaccinatum and certain cases of progressive vaccinia. However, VIG is contraindicated for the treatment of vaccinial keratitis. VIG is recommended for severe generalized vaccinia if the patient is extremely ill or has a serious underlying disease. VIG provides no benefit in the treatment of postvaccinal encephalitis and has no role in the treatment of smallpox. Current supplies of VIG are limited, and its use should be reserved for treatment of vaccine complications with serious clinical manifestations. The recommended dosage of the currently available VIG for treatment of complications is 0.6 ml/kg of body weight. VIG must be administered intramuscularly and should be administered as early as possible after the onset of symptoms. Because therapeutic doses of VIG might be substantial (e.g., 42 ml for a person weighing 70 kg), the product should be administered in divided doses over a 24- to 36-hour period. Doses can be repeated, usually at intervals of 2–3 days, until recovery begins (e.g., no new lesions appear). Future reformulations of VIG might require intravenous administration, and health-care providers should refer to the manufacturer's package insert for correct dosages and route of administration. CDC is currently the only source of VIG for civilians (see Vaccinia Vaccine Availability for contact information). The Food and Drug Administration has not approved the use of any antiviral compound for the treatment of vaccinia virus infections or other Orthopoxvirus infections, including smallpox.
Certain antiviral compounds such as tecovirimat (ST-246) have been reported to be 100% active against vaccinia virus or other Orthopoxviruses in vitro and among test animals. Tecovirimat has been granted orphan drug status by the FDA and is currently under study to determine the safety and effectiveness in humans.
Imatinib, a compound FDA approved for cancer treatment limits the release of enveloped extracellular virions and protects mice from a lethal challenge with vaccinia. Currently, imatinib and related compounds are being evaluated by the CDC for their efficacy against smallpox and monkeypox. Questions also remain regarding the effective dose and the timing and length of administration of these antiviral compounds. Insufficient information exists on which to base recommendations for any antiviral compound to treat post-vaccination complications or Orthopoxvirus infections, including smallpox. However, additional information could become available, and health-care providers should consult CDC to obtain up-dated information regarding treatment options for smallpox vaccination complications (see Consultation Regarding Complications of Vaccinia Vaccine).
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