Viruses poxvirus

DNA viruses Poxviruses Variola Vaccinia Large particles 200 x 250nm complex symmetry Variola is the smallpox virus. It produces a systemic infection with a characteristic vesicular rash affecting the face, arms and legs, and has a high mortality rate. Vaccinia has been derived from the cowpox virus and is used to immunize against smallpox... 

All laboratory personnel working with the agent must have documented polio vaccinations or demonstrated evidence of immunity to all three types of polio virus Poxviruses... 

The feature common to the cytotoxic effects brought on by nonreplicating influenza virus, poxvirus, and defective-interfering vesicular stomatitis virus is the high multiplicity of infection required. This has led to the assumption that the toxic effect is caused by one or more components of the parental input virion, most likely protein in origin. However, Cordell-Stewart and Taylor (1971, 1973) have provided evidence that the double-stranded viral RNA isolated from cells infected with bovine enterovirus causes a rapid cytopathic effect as determined by trypan-blue uptake or Cr release from affected Ehrlich ascites tumor cells or L1210 cells toxic effects are reduced or do not occur in cells exposed to single-stranded or heat-denatured double-stranded viral RNA and the toxic effect of bovine enteroviral double-stranded RNA is not abolished by inhibitors of protein synthesis such as puromycin or cycloheximide. 

However, acyclic nucleotide analogs (acyclic nucleoside phosphonates) have been developed, which carry one phosphonate moiety and require only the two subsequent phosphorylation steps (De Clercq et al. 1978). Independent of virus-encoded kinases, they display a broader spectrum of efficacy. This class comprises important drugs against HIV (tenofovir) and HBV (adefovir, tenofovir), as well as cidofovir, which is approved for use against CMV retinitis, but also displays an exceptionally broad efficacy profile against many herpesviruses, adenovirus, poxviruses, and papillomaviruses (De Clercq and Holy 2005). 

Cidofovir (Fig. 2) has been formally approved for the treatment of CMV retinitis in AIDS patients, where it is administered intravenously at a dose not exceeding 5 mg/kg once weekly during the first two weeks (and every other week thereafter). Cidofovir is also used off label for the treatment of human papilloma virus (HPV) infections (i.e., cutaneous warts, anogenital warts, laryngeal and pharyngeal papilloma), polyomavirus [i.e., progressive (i.e., multifocal leukoencephalopathy (PML)], adenovirus, herpesvirus, and poxvirus (i.e., molluscum contagiosum) infections, where it can be administered intravenously (at a dose of < 5 mg/kg once weekly or every other week) or topically as a 1% gel or cream (De Clercq and Holy 2005). Especially in immunosuppressed patients (i.e., transplant recipients), local treatment of HPV-associated lesions has often yielded spectacular results (Bonatti etal.2007). 

Whereas a bacterial cell like a staphylococcus might be lOOOnm in diameter, the largest of the human pathogenic viruses, the poxviruses, measure only 250 nm along their longest axis, and the smallest, the poliovirus, is only 28 nm in diameter. They are mostly, therefore, beyond the limit of resolution of the light microscope and have to be visualized with the electron microscope. 

There is a third structural group comprising the poxviruses and many bacterial viruses, in which a number of major structural components can be identified and the overall geometry of the particles is complex. 

Virus genera are designated by terms ending in - virus. Thus, among the Poxviridae those poxviruses which infect fowl are called by the genus name Avipoxvirus. Note that frequently in the animal viruses, the genus is defined based on the host which the virus infects. 

Darai G, Moss B. The genome of mol-luscum contagiosum virus analysis and comparison with other poxviruses. Virology 1997 23 3(1] 19—42. 

Most vaccine vectors developed to date are viral based, with poxviruses (as well as picorna viruses and adenoviruses) being used most. In general, such recombinant viral vectors elicit both... 

Li+ has significant inhibitory effects upon DNA viruses, in particular HSV which has been studied in depth. It was originally shown that Li+ inhibits viral replication in a dose-dependent, reversible manner in HSV-infected baby hamster kidney cells [240], and this has been found to be due to a Li+-induced decrease in the synthesis of viral DNA [241]. It is now well established that Li+ inhibits DNA synthesis in HSV types 1 and 2 and in several other DNA viruses, including measles, vaccinia, adenovirus, poxvirus, pseudorabies virus, Epstein-Barr virus, and the bovine, equine, and canine HV s [241]. Interestingly, Li+ has no effect on the replication of RNA viruses, such as influenza or encephalomyo-carditis virus. 

Vaccines Vaccinia virus is a live poxvirus that can lead to strong cross-protection to smallpox for about five years, plus partial protection for ten or more years. If your are old enough, or have been in military service in recent years, you may have been vaccinated with this vaccine administered by dermal scarification, or intra-dermal jet injection. However, certain persons should NOT receive smallpox vaccine, including persons who are pregnant, persons who underwent a clinical immunosuppresion, persons with eczema, or persons with leukemia or lymphoma. 

Feuh, K., et ah. Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses. Virus Res, 2002, 88(1-2), 55-69. 

Following their production, the viral components are assembled to form a mature virus particle. The viral genome is encapsulated by viral protein in some cases (e.g. adenovirus, poliovirus), it is not encapsulated. In certain viruses, such as the poxviruses, multiple membranes surround the capsid. Release of the virus from the host cell may be rapid and produce cell lysis and death. A slower process resembling budding may allow the host cell to survive. 

Vidarabine (adenine arabinoside, Vira-A) is an adenine nucleoside analogue containing arabinose in place of ri-bose. It is obtained from cultures of Streptomyces an-tibioticus and has activity against HSV-1, HSV-2, VZV, CMV, HBV, poxviruses, hepadnaviruses, rhabdoviruses, and certain RNA tumor viruses. 

There is a wide variety of vectors used to deliver DNA or oligonucleotides into mammalian cells, either in vitro or in vivo. The most common vector systems are based on viral [retroviruses (9, 10), adeno-associated virus (AAV) (11), adenovirus (12, 13), herpes simplex virus (HSV) (14)] andnonviral [cationic liposomes (15,16), polymers and receptor-mediated polylysine-DNA] complexes (17). Other viral vectors that are currently under development are based on lentiviruses (18), human cytomegalovirus (CMV) (19), Epstein-Barr virus (EBV) (20), poxviruses (21), negative-strand RNA viruses (influenza virus), alphaviruses and herpesvirus saimiri (22). Also a hybrid adenoviral/retroviral vector has successfully been used for in vivo gene transduction (23). A simplified schematic representation of basic human gene therapy methods is described in Figure 13.1. 

The oncolytic viruses include adenovirus, measles, reovirus, vesicular stomatitis virus (VSV),HSV,poxvirus, and vaccinia. Specific examples include (1) ONYX-015, which is an adenoviral oncolytic virus, administered to patients with liver metastases of colorectal cancer and pancreatic cancer [29], (2) Reolysin, which is an oncolytic reovirus administered to patients with glioma [30], and (3) MV-CEA, which is an oncolytic measles virus expressing carcinoembryonic antigen, administered to patients with ovarian cancer [31]. Some oncolytic viruses are wild type and are apparently not pathogenic in humans, such as the Newcastle disease virus (NDV), which is an RNA avian paramyxovirus. PV701, a naturally attenuated, replication-competent strain of NDV, has been administered to patients with advanced solid tumors [32], The applicability of oncolytic viruses as a therapy for clinical oncology trials is due to their potential selectivity the ability to kill tumor cells but not normal cells. However, the level of attenuation of viral replication in normal cells is limited for most oncolytic vectors. 

Viruses, especially large DNA viruses like poxviruses and herpesviruses, have evolved several mechanisms to evade, subvert, and manipulate the host immune system, ensuring their survival and spread (Murphy, 2001 Nash... 

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