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 its species Lake Victoria marburgvirus. However, most scientific articles continued to refer to Marburg virus. Consequently, in 2010, the name Marburg virus was reinstated and the species name changed. 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.
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:
? (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)
Like all mononegaviruses, marburgvirions contain non-infectious, linear nonsegmented, single-stranded RNAgenomes 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.
CryoEM reconstruction of a section of the Marburg virus nucleocapsid. EMDB entry EMD-1986
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 helicalribonucleocapsid, 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.
Niemann–Pick C1 (NPC1) appears to be essential for Ebola and Marburg virus infection. Two independent studies reported in the same issue of Nature (journal) showed that Ebola virus cell entry and replication requires the cholesterol transporter protein NPC1. When cells from Niemann Pick Type C1 patients were exposed to Ebola virus in the laboratory, the cells survived and appeared immune to the virus, further indicating that Ebola relies on NPC1 to enter cells. This might imply that genetic mutations in the NPC1 gene in humans could make some people resistant to one of the deadliest known viruses affecting humans. The same studies described similar results with Ebola's cousin in the filovirus group, Marburg virus, showing that it too needs NPC1 to enter cells. Furthemore, NPC1 was shown to be critical to filovirus entry because it mediates infection by binding directly to the viral envelope glycoprotein. A later study confirmed the findings that NPC1 is a critical filovirus receptor that mediates infection by binding directly to the viral envelope glycoprotein and that the second lysosomal domain of NPC1 mediates this binding.
In one of the original studies, a small molecule was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1. In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse adapted Ebola virus. Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola anti-viral drug.
The marburg virus 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.
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. Recently the first experimental infection study of Rousettus aegyptiacus with MARV provided further insight into the possible involvement of these bats in MARV ecology. Experimentally infected bats developed relatively low viremia lasting at least 5 days, but remained healthy and didn't develop any notable gross pathology. The virus also replicated to high titers in major organs (liver and spleen), and organs that might possibly be involved in virus transmission (lung, intestine, reproductive organ, salivary gland, kidney, bladder and mammary gland). The relatively long period of viremia noted in this experiment could possibly also facilitate mechanical transmission by blood sucking arthropods or infection of susceptible vertebrate hosts by direct contact with infected blood.
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 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.
In the TV series Body of Proof, Season 2, episodes 18 and 19 include a MARV outbreak.
In Mira Grant's novel Feed, a modified Marburg virus that cures cancer combines with a virally transmitted cure for the common cold, resulting in a virulent viral plague that turns infected humans and animals into zombies.
Motaba, the fictional deadly viral hemorrhagic fever, in the movie Outbreak, is based on MARV
In the video game Trauma Team, the seventh chapter of the game, named "Patient Zero", has a storyline of a mass outbreak of the fictional Rosalia Virus, which has similar symptoms to the Ebola Virus and Marburg Virus.
In the TV show Leverage, a weaponized Marburg virus made by the Soviets is used on the team's mark in "The Order 23 Job".
In the episode "Death is in the Air" of the TV show Psych, the fictional Thornburg virus is based on the Marburg virus.
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