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Bio-Terror Agents

    MARBURG VIRUS (MARV)

    BIOTERRORBIBLE.COM: There is an ever expanding list of potential bio-terror agents that could be used in a bio-terror attack, but anthrax, smallpox and flu are the only “threats” the government appears worried about. These 3 agents will likely be used the same way that they were used in the U.S. government bio-terror war-games entitled Dark Winter and Atlantic Storm.

    Title: Marburg Virus
    Date:
    2012
    Source:
    Wikipedia

    Abstract: The Marburg virus in the Filoviridae family was first noticed and described during a small epidemic in the city of Marburg, Germany. Workers were accidentally exposed to infected green monkey tissue at the city's former main industrial plant, the Behring-Werke, then part of Hoechst, and today of CSL Behring. The plant was founded by Marburg citizen and first Nobel Prize in Physiology or Medicine winner, Emil Adolf von Behring. During the outbreak, 31 people became infected and seven of them died. "Marburg virus" is named after the city, consistent with the custom of naming hemorrhagic fever viruses after the location of their first recorded outbreak.

    Marburg virus (MARV) causes severe disease in humans and nonhuman primates in the form of viral hemorrhagic fever. MARV is a select agent,[1] WHO risk group 4 pathogen (requiring biosafety level 4-equivalent containment), NIH/National Institute of Allergy and Infectious Diseases category A priority pathogen, Centers for Disease Control and Prevention Category A Bioterrorism Agent, and is listed as a biological agent for export control by the Australia Group.

    Use of Term
    Marburg virus was first described in 1967. Today, the virus is one of two members of the
    species Marburg marburgvirus, which is included into the genus Marburgvirus, family Filoviridae, order Mononegavirales. The name Marburg virus is derived from Marburg (the city in Hesse, West Germany, where the virus was first discovered) and the taxonomic suffix virus.

    Note
    Marburg virus is pronounced ˌmɑrbərg vɑɪrəs (IPA) or mahr-berg vahy-ruhs in English phonetic notation. According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Marburg virus is always to be capitalized, but is never italicized, and may be abbreviated (with MARV being the official abbreviation).

    Previous Designations
    Marburg virus was first introduced under this name in 1967. In 2005, the virus name was changed to Lake Victoria marburgvirus, which unfortunately was the same spelling as the species Lake Victoria marburgvirus. However, most scientific articles continued to refer to Marburg virus. Consequently, in 2010, the name Marburg virus was reinstated. A previous abbreviation for the virus was MBGV.

    Virus Inclusion Criteria
    A virus that fulfills the criteria for being a member of the species Marburg marburgvirus is a Marburg virus if its genome diverges from that of the prototype Marburg marburgvirus, Marburg virus variant Musoke (MARV/Mus), by <10% at the nucleotide level.

    Disease
    Main article: Marburg virus disease

    MARV is one of two marburgviruses that causes Marburg virus disease (MVD) in humans (in the literature also often referred to as Marburg hemorrhagic fever, MHF). In the past, MARV has caused the following MVD outbreaks:

    Marburg Virus Disease (MVD) Outbreaks Due to Marburg Virus (MARV) Infection

    Year-Location-Human/DeathsCases (case-fatality rate)

    1.
    1967: Marburg and Frankfurt, West Germany, and Belgrade, Yugoslavia: 7/31 (23%)
    2. 1975: Rhodesia and Johannesburg, South Africa: 1/3 (33%)
    3. 1980: Kenya: 1/2 (50%)
    4. 1987: Kenya: 1/1 (100%)
    5. 1988: Koltsovo, Soviet Union: 1/1 (100%) [Laboratory Accident]
    6. 1990: Koltsovo, Soviet Union: 0/1 (0%) [Laboratory Accident]
    7. 1998: Durba and Watsa, Democratic Republic of the Congo: ? (A total of 154 cases and 128 deaths of marburgvirus infection were recorded during this outbreak. The case fatality was 83%. Two different marburgviruses, MARV and
    Ravn virus (RAVV), cocirculated and caused disease. It has never been published how many cases and deaths were due to MARV or RAVV infection)
    8. 2004-2005: Angola: 227/252 (90%)
    9. 2007: Uganda: 1/3 (33%)
    10. 2008: Uganda: 1/1 (100%)

    Virology

    Genome
    Like all mononegaviruses, marburgvirions contain non-infectious, linear nonsegmented, single-stranded RNA genomes of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a 5' cap, are not polyadenylated, and are not covalently linked to a protein. Marburgvirus genomes are approximately 19 kb long and contain seven genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR. The genomes of the two different marburgviruses (MARV and RAVV) differ in sequence.

    Structure

    Like all filoviruses, marburgvirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched. Marburgvirions are generally 80 nm in width, but vary somewhat in length. In general, the median particle length of marburgviruses ranges from 795–828 nm (in contrast to ebolavirions, whose median particle length was measured to be 974–1,086 nm ), but particles as long as 14,000 nm have been detected in tissue culture. Marburgvirions consist of seven structural proteins. At the center is the helical ribonucleocapsid, which consists of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane derived from the host cell membrane. The membrane anchors a glycoprotein (GP1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions in structure, marburgvirions are antigenically distinct.

    Replication
    The marburgvirus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The virus RdRp partially uncoats the nucleocapsid and transcribes the genes into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Marburgvirus L binds to a single promoter located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.

    Ecology
    In 2009, the successful isolation of infectious MARV was reported from caught healthy Egyptian rousettes (Rousettus aegyptiacus). This isolation, together with the isolation of infectious RAVV, strongly suggests that Old World fruit bats are involved in the natural maintenance of marburgviruses. Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts.

    Weaponization
    The Soviet Union had an extensive offensive and defensive biological weapons program that included MARV. At least three Soviet research institutes had MARV research programs during offensive times: the Virology Center of the Scientific-Research Institute for Microbiology in Zagorsk (today Sergiev Posad), the Scientific-Production Association "Vektor" (today the State Research Center of Virology and Biotechnology "Vektor") in Koltsovo, and the Irkutsk Scientific-Research Anti-Plague Institute of Siberia and the Far East in Irkutsk. As most performed research was highly classified, it remains unclear how successful the MARV program was. However, Soviet defector Ken Alibek claimed that a weapon filled with MARV was tested at the Stepnogorsk Scientific Experimental and Production Base in Stepnogorsk, Kazakh Soviet Socialist Republic (today Kazakhstan),[41] suggesting that the development of a MARV biological weapon had reached advanced stages. Independent confirmation for this claim is lacking. At least one laboratory accident with MARV, resulting in the death of Koltsovo researcher Nikolai Ustinov, occurred during offensive times in the Soviet Union and was first described in detail by Alibek. After the collapse of the Soviet Union, MARV research continued in all three institutes, but judging from published material this research has been defensive in nature.

    Popular Culture

    In the non-fiction thriller, The Hot Zone, Richard Preston describes several MARV infections

    In the TV series Millennium, at the end of Season 2, a "prion version" of MARV causes a disease outbreak in Seattle, killing (amongst others) Frank Black's wife, Catherine. In the Season 3 episode Collateral Damage, Peter Watt's daughter is infected with MARV by a Gulf War veteran who claims that the Millennium Group did the same to American soldiers during the first Gulf War

    In the crossover event of the TV series Medical Investigation, episode 17, and Third Watch, season 6 episode 16, Marburg virus disease breaks out in New York City, killing 5 of 6 infected people

    In the Sarah Jane Smith series (Series Two), MARV is used as a weapon by a doomsday cult

    In the short story Hell Hath Enlarged Herself by Michael Marshall Smith, one of the original scientists is infected with MARV in an attempt to test ImmunityWorks ver. 1.0

    In the novel Microserfs by Douglas Coupland, MARV is mentioned several times as a metaphor for the spread of information through the internet

    In the novel Resident Evil: Caliban Cove an insane scientist and former professor named Nicolas Griffith is referred to by Rebecca Chambers as having infected three men with MARV after they had been led to believe it was a harmless common cold virus

    In the novel Pandora's Legion by Harold Coyle and Barrett Tillman, an Al-Qaeda cell in Pakistan injects volunteers with MARV, who then board flights to major international airports in the western world where the large flow of people would facilitate the spreading of the virus into a pandemic (Wikipedia, 2012).