Vaccinia viruses

Vaccinia virus Vaccinology Vacodur 16 Vacoflux Z Vacoperm 100... 

Rodriguez, J. F., et al. (1988). Expression of the firefly luciferase gene in vaccinia virus a highly sensitive gene marker to follow virus dissemination in tissues of infected animals. Proc. Natl. Acad. Sci. USA 85 1667-1671. 

Hamre D, Brownlee KA, Donovick R (1951) Studies on the chemotherapy of vaccinia virus. II. The activity of some thiosemicarbazones. J Immunol 67 305-312... 

Taylor JM, QuUty D, Banadyga L, Barry M (2006) The vaccinia virus protein FIL interacts with Bim and inhibits activation of the pro-apoptotic protein Bax. The Journal of biological chemistry 281 39728-39739... 

Quenelle DC, Collins DJ, Wan WB, Beadle JR, Hostetler KY, Kern ER (2004) Oral treatment of cowpox and vaccinia virus infections in mice with ether Upid esters of ddofovir. Antimicrob Agents Chemother 48 404-412... 

Verini, M.A. and M. Ghione. Activity of distamycin A on vaccinia virus infection of cell cultures. Chemotherapia 1964, 9, 144-157. 

Virus replication comprises numerous biochemieal transformations that might provide suitable targets for antiviral therapy. The antiviral effect of thiosemicarbazones was first demonstrated by Hamre et al. [53, 54], who showed that p-aminobenzaldehyde-3-thiosemicarbazone and several of its derivatives were active against vaccinia virus in mice. These studies were extended to include thiosemicarbazones of isatin, benzene, thiophene, pyridine, and quinoline derivatives, which also showed activity against vaccinia-induced encephalitis. The nature of the aldehyde/ketone moiety was not as significant as the presence of the thiosemicarbazide side chain the latter was deemed essential for antiviral activity. 

Komano J, Miyauchi K, Matsuda Z, Yamamoto N. Inhibiting the Arp2/3 complex limits infection of both intracellular mature vaccinia virus and primate lentivi-ruses. Mol Biol Cell 2004 15(12) 5197-5207. 

As discussed above, alternative recombinant DNA techniques are necessary to efficiently generate genome-scale clone sets. One alternative exploits the ability of the Vaccinia virus DNA topoisomerase I to both cleave and rejoin DNA strands with high sequence specificity (Shuman, 1992a Shuman, 1992b). In the reaction, the enzyme recognizes the sequence 5 -CCCTT and cleaves at the final T whereby a covalent adduct is formed between the 3 phosphate of the cleaved strand and a tyrosine residue in the enzyme (Fig. 4.1). The covalent complex can combine with a heterologous acceptor DNA that has a 5 hydroxyl tail complementary to the sequence on the covalent adduct to create a recombinant molecule (Shuman, 1994). 

Figure 4.1. Vaccinia virus topoisomerase I reaction with DNA to form a covalent adduct. Figure adapted from Heyman et al. (1999).

Figure 4.4. Schematic illustration of directional topoisomerase cloning of PCR products into the pUNI vector. The PCR product to be cloned has the sequence 5 -CACC appended at the 5 end to direct the orientation of cloning. The Vaccinia virus topoisomerase I enzyme forms a covalent adduct with the cloning vector to create a cloning competent plasmid construct. The loxP site is 5 to the insertion site. The vector and PCR product are designed to fuse the ORF in-frame with loxP.

McCraith, S., Holtzman, T., Moss, B., and Fields, S. (2000). Genome-wide analysis of vaccinia virus protein-protein interactions. Proc. Natl. Acad. Sci USA 97, 4879-4884. 

McCraith S et al. Genome-wide analysis of vaccinia virus protein-protein interactions. Proc Natl Acad Sci USA 2000 97 4879-4884. 

A number of factors render vaccinia virus a particularly attractive vector system. These include ... 

Cdc, cell division cycle DARPP-32, dopamine and cAMP-regulated phosphoprotein of 32kDa MAPK, mitogen-activated protein kinase NIPP1, nuclear inhibitor of PP1 PP, protein phosphatase Vffl, vaccinia virus. 

Mitogen-activated protein kinase phosphatases are dual-function protein phosphatases. Just as the MAPK kinases (e.g. MEKs) are unique as dual-functioning kinases in that they phosphorylate MAPKs on threonine and tyrosine residues, there are unique dual-function ing protein phosphatases that reverse the phosphorylation and activation of MAPKs [43], Such MAPK phosphatases (MKPs) were first identified as a product of vaccinia virus (VH1) and later found in all eukaryotic cells. There are now numerous members of this VH1 family of dual-functioning protein phosphatases. 

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. 

No, smallpox vaccine does not contain smallpox virus but another live virus called vaccinia virus. Since this virus is related to smallpox virus, vaccination with vaccina provides immunity against infection from smallpox virus. 

The vaccine against smallpox is made with a virus related to smallpox virus called vaccinia virus. It is not made with smallpox virus called variola. The vaccine is a highly effective immunizing agent against smallpox infection. It was successfully used to eradicate smallpox from the human population. 

Yes. Vaccinia vaccine is recommended for laboratory workers who directly handle cultures, animals contaminated or infected with, nonhighly attenuated vaccinia virus, recombinant vaccinia viruses derived from nonhighly attenuated vaccinia strains, or other orthopoxviruses that infect humans. These would include monkeypox, cowpox, vaccinia, and variola. Other health-care workers, such as physicians and nurses whose contact with nonhighly attenuated vaccinia viruses is limited to contaminated materials such as medical dressings but who adhere to appropriate infection control measures, are at lower risk for accidental infection than laboratory workers. However, because a theoretical risk for infection exists, vaccination can be offered to this group. Vaccination is not recommended for people who do not directly handle nonhighly attenuated virus cultures or materials or who do not work with animals contaminated or infected with these viruses. 

In addition to the stock of smallpox vaccine in the US, an additional 50-100 million doses are estimated to exist worldwide. Many countries still hold smallpox vaccine (vaccinia) stocks. WHO recommends that countries that still have stocks of smallpox vaccine (vaccinia) maintain these stocks. This recommendation has been made for two reasons. Firstly, small amounts of vaccine are still needed to vaccinate laboratory personnel handling vaccinia virus and other members of this virus family. Some of these viruses are found in nature and cause illness among animals, and some are used in research to make new, safer vaccines against a variety of infectious diseases. Secondly, smallpox vaccine, vaccinia, will also be needed in case of a deliberate or accidental release of smallpox virus, variola. 

M.J. Espy, J.R. Uhl, L.M. Sloan, J.E. Rosenblatt, F.R. Cockerill and T.F. Smith, Detection of Vaccinia virus, Herpes Simplex virus, Varicella-Zoster... 

Nezu J, Oku A, Jones MH, Shimane M (1997) Identification of two novel human putative serine/threonine kinases, VRKl and VRK2, with structural similarity to vaccinia virus BIR kinase. Genomics... 

Injection of recombinant vaccinia virus carrying cDNA of the protein of interest driven by an early promoter has proven successful (Yang et al., 1991). This method precludes the need to synthesize cRNA in vitro. 

Yang XC, Karschin A, Labarca C, Elroy-Stein O, Moss B, et al. 1991. Ejq)ression of ion channels and receptors in Xenopus oocytes using vaccinia virus. FASEB J 5 (8) 2209. 

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