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07-SEPTEMBER-2008 03:17:44 - Vaccinia This article or section may contain inappropriate or misinterpreted citations that do not verify the text. by checking for inaccuracies. May 2008 help, talk, get involved! Vaccinia virus A TEM micrograph of Vaccinia virus virions. A TEM micrograph of Vaccinia virus virions. Virus classification Group: Group I dsDNA Family: Poxviridae Genus: Orthopoxvirus Species: Vaccinia virus Vaccinia Classification and external resources ICD-10 B08.0 ICD-9 051.0 eMedicine med/2356 MeSH D014615 Vaccinia virus VACV or VV is a large, complex, enveloped virus belonging to the poxvirus family.1 It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm. Vaccinia virus is well-known for its role as a vaccine that eradicated the smallpox disease, making it the first human disease to be successfully eradicated by mankind. This endeavour was carried out by the World Health Organization under the Smallpox Eradication Program. Post eradication of smallpox, scientists study Vaccinia virus to use as a tool for delivering genes into biological tissues gene therapy and genetic engineering. Moreover, due to recent concerns about smallpox resurfacing as a possible agent for bioterrorism, scientists have renewed their interests in studying Vaccinia virus. Contents 1 Origin 2 Basic biology 3 Host resistance 4 Use as a vaccine 5 History 6 Recent cases 7 References 7.1 Further reading 8 External links Origin Vaccinia virus is closely related to the virus that causes Cowpox; historically the two were often considered to be one and the same.2 The precise origin of Vaccinia virus is unknown, however, due to the lack of record-keeping as the virus was repeatedly cultivated and passaged in research laboratories for many decades.3 The most common notion is that Vaccinia virus, Cowpox virus, and Variola virus the causative agent of smallpox, were all derived from a common ancestral virus. There is also speculation that Vaccinia virus was originally isolated from horses.2 Basic biology Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus.4 Therefore, the large genome is required for encoding various enzymes and proteins involved in viral DNA replication and gene transcription. During its replication cycle, VV produces four infectious forms which differ in their outer membranes: intracellular mature virion IMV, the intracellular enveloped virion IEV, the cell-associated enveloped virion CEV and the extracellular enveloped virion EEV.5 Although the issue remains contentious, the prevailing view is that the IMV consists of a single lipoprotein membrane, while the CEV and EEV are both surrounded by two membrane layers and the IEV has three envelopes. The IMV is the most abundant infectious form and is thought to be responsible for spread between hosts. On the other hand, the CEV is believed to play a role in cell-to-cell spread and the EEV is thought to be important for long range dissemination within the host organism. Host resistance Vaccinia contains within its genome several proteins that give the virus resistance to interferons. K3L is a protein with homology to the protein eukaryotic initiation factor 2 eIF-2alpha. K3L protein inhibits the action of PKR, an activator of interferons. E3L is another protein encoded by Vaccinia. E3L also inhibits PKR activation; and is also able to bind to double stranded RNA.6 Use as a vaccine Site of a vaccinia injection, several days later. Site of a vaccinia injection, several days later. A Vaccinia virus infection is very mild and is typically asymptomatic in healthy individuals, but it may cause a mild rash and fever. Immune responses generated from a Vaccinia virus infection protects the person against a lethal smallpox infection. For this reason, Vaccinia virus was, and is still being used as a live-virus vaccine against smallpox. Unlike vaccines that use weakened forms of the virus being vaccinated against, the Vaccinia virus vaccine cannot cause a smallpox infection because it does not contain the smallpox virus. However, certain complications and/or vaccine adverse effects occasionally arise. The chance of this happening is significantly increased in people who are immunocompromised. Approximately one in one million individuals will develop a fatal response to the vaccination. Currently, the vaccine is only administered to health care workers or research personnel who have a high risk of contracting Vaccinia virus, and to the military personnel of the United States of America. Due to the present threat of smallpox-related bioterrorism, there is a possibility the vaccine may have to be widely administered again in the future. Therefore, scientists are currently developing novel vaccine strategies against smallpox which are safer and much faster to deploy during a bioterrorism event. On September 1, 2007, the U.S. Food and Drug Administration FDA licensed a new vaccine ACAM2000 against smallpox which can be produced quickly upon need. Manufactured by Acambis of Cambridge, England, and Cambridge, Massachusetts, the U.S. Centers for Disease Control and Prevention stockpiled 192.5 million doses of the new vaccine derived from the old Dryvax, and made using a pox virus vaccinia.7 History The original vaccine for smallpox, and the origin of the idea of vaccination, was Cowpox, reported on by Edward Jenner in 1796.3 The Latin term used for Cowpox was variolae vaccinae, essentially a direct translation of cow-related pox. That term lent its name to the whole idea of vaccination. When it was realized that the virus used in smallpox vaccination was not, or was no longer, the same as the Cowpox virus, the name 'vaccinia' stayed with the vaccine-related virus. See OED. Recent cases In March 2007, a 2-year-old Indiana boy and his mother contracted the life-threatening vaccinia infection from the boy's father.8 The boy developed the telltale rash over 80 percent of his body after coming into close contact with his father, who was vaccinated for smallpox before being deployed overseas by the United States Army. The United States military resumed smallpox vaccinations in 2002. The child acquired the infection due to eczema, which is a known risk factor for vaccinia infection. The boy was treated with intravenous immunoglobulin, cidofovir, and an experimental drug being developed by SIGA Technologies9. On April 19, 2007, he was sent home with no after effects except for possible scarring of the skin.8 References ^ Ryan KJ, Ray CG ors 2004. Sherris Medical Microbiology, 4th ed., McGraw Hill. ISBN 0-8385-8529-9. ^ a b Huygelen C 1996. Jenner's cowpox vaccine in light of current vaccinology in Dutch; Flemish. Verh. K. Acad. Geneeskd. Belg. 58 5: 479-536; discussion 537-8. PMID 9027132. ^ a b Henderson DA, Moss B 1988 1999. Smallpox and Vaccinia, in Plotkin SA, Orenstein WA: Vaccines, 3rd ed, Philadelphia, Pennsylvania: WB Saunders. ISBN 0-7216-7443-7. Retrieved on 2007-07-25. ^ Tolonen N, Doglio L, Schleich S, Krijnse Locker J 2001. Vaccinia virus DNA replication occurs in endoplasmic reticulum-enclosed cytoplasmic mini-nuclei. Mol. Biol. Cell 12 7: 2031-46. PMID 11452001. ^ Smith GL, Vanderplasschen A, Law M 2002. The formation and function of extracellular enveloped Vaccinia virus. J. Gen. Virol. 83 Pt 12: 2915-31. PMID 12466468. ^ Davies MV, Chang HW, Jacobs BL, Kaufman RJ 1993. The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms. J. Virol. 67 3: 1688-92. PMID 8094759. ^ Canadian Press, FDA licenses new vaccine against smallpox; can be produced quickly if needed ^ a b Centers for Disease Control and Prevention CDC 2007. Household transmission of vaccinia virus from contact with a military smallpox vaccinee--Illinois and Indiana, 2007. Morbidity and Mortality Weekly Report 56 19: 478-81. PMID 17510612. ^ SIGA Technologies 2007-03-17. SIGA's Smallpox Drug Candidate Administered to Critically Ill Human Patient. Press release. Retrieved on 2007-06-05. Further reading Gubser C, Hué S, Kellam P, Smith GL January 2004. Poxvirus genomes: a phylogenetic analysis. J Gen Virol 85 1: 105-17. doi:10.1099/vir.0.19565-0. PMID 14718625. Centers for Disease Control and Prevention CDC 2007. Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee--Alaska, 2006. MMWR Morb. Mortal. Wkly. Rep. 56 17: 417-9. PMID 17476203. External links Vaccinia virus, complete genome. National Center for Biotechnology Information. Retrieved on 2007-07-25. Condit RC, Moussatche N, Traktman P. The Vaccinia Virion: 3D Tour. Retrieved on 2007-07-26. Smallpox. Emergency Preparedness Response. Centers for Disease Control and Prevention. Retrieved on 2007-07-26. v d e Infectious diseases - Virus diseases A80-B34, 042-079 CNS Encephalitis/ meningitis DNA virus: Progressive multifocal leukoencephalopathy RNA virus: Subacute sclerosing panencephalitis - Lymphocytic choriomeningitis - Tick-borne meningoencephalitis unknown: Encephalitis lethargica Eye DNA virus: Cytomegalovirus retinitis Other RNA virus: Rabies - Myelitis: Poliomyelitis Post-polio syndrome - Tropical spastic paraparesis Skin and mucous membrane lesions DNA virus, Herpesviridae: Herpes simplex - Chickenpox - Herpes zoster - KSHV DNA virus, other: Poxviridae Smallpox, Monkeypox, Cowpox, Vaccinia, Molluscum contagiosum - exanthem Roseola, Fifth disease - HPV Wart RNA virus: exanthem Measles, Rubella - picornavirus Hand, foot and mouth disease, Foot-and-mouth disease Digestive system Hepatitis DNA virus: B RNA virus: A - D - C - E - G Gastroenteritis DNA virus: Adenovirus RNA virus: Rotavirus - Norovirus - Astrovirus - Coronavirus Respiratory system RNA virus, IV: Acute viral nasopharyngitis - Severe acute respiratory syndrome RNA virus, V: Influenza/Avian influenza - Human parainfluenza viruses - RSV - hMPV Other/varied: Infectious mononucleosis - Viral pneumonia Sexually transmitted DNA virus: HPV Genital warts, Cervical cancer RNA virus, retrovirus: HIV AIDS, AIDS dementia complex - Adult T-cell leukemia Oncovirus DNA virus: Hepatitis B - HPV - Kaposi's sarcoma-associated herpesvirus RNA virus: Hepatitis C - HTLV Systemic DNA virus: Cytomegalovirus RNA virus: Mumps - Bornholm disease - Coxsackie B Retrieved from http://en..org/wiki/Vaccinia Categories: Infectious diseases | PoxvirusesHidden categories: Articles lacking sources from May 2008 | All articles lacking sources Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Français This page was last modified on 20 June 2008, at 16:02
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