Marburgvirus
Marburg Virus Disease
Filoviridae
Ebolavirus
The nucleoprotein of Marburg virus is target for multiple cellular kinases. (1/182)
The nucleoprotein (NP) of Marburg virus is phosphorylated at serine and threonine residues in a ratio of 85:15, regardless of whether the protein is isolated from virions or from eukaryotic expression systems. Phosphotyrosine is absent. Although many potential phosphorylation sites are located in the N-terminal half of NP, this part of the protein is not phosphorylated. Analyses of phosphorylation state and phosphoamino acid content of truncated NPs expressed in HeLa cells using the vaccinia virus T7 expression system led to the identification of seven phosphorylated regions (region I*, amino acids 404-432; II*, amino acids 446-472; III*, amino acids 484-511; IV*, amino acids 534-543; V*, amino acid 549; VI*, amino acids 599-604; and VII*, amino acid 619) with a minimum of seven phosphorylated amino acid residues located in the C-terminal half of NP. All phosphothreonine residues and consensus recognition sequences for protein kinase CKII are located in regions I*-V*. Regions VI* and VII* contain only phosphoserine with three of four serine residues in consensus recognition motifs for proline-directed protein kinases. Mutagenesis of proline-adjacent serine residues to alanine or aspartic acid did not influence the function of NP in a reconstituted transcription/replication system; thus it is concluded that serine phosphorylation in the most C-terminal part of NP is not a regulatory factor in viral RNA synthesis. (+info)Proteolytic processing of Marburg virus glycoprotein. (2/182)
Processing of the transmembrane glycoprotein (GP) of Marburg virus involved the conversion of an endo H-sensitive, ER-specific form into an endo H-resistant, Golgi-specific precursor that was cleaved into GP(1) and GP(2). Cleavage was mediated by furin or another subtilisin-like endoprotease with similar substrate specificity as indicated by mutational analysis of the cleavage site and inhibition using peptidyl chloromethylketones. Mature GP consisted of disulfide-linked GP(1) and GP(2) subunits. (+info)Ultrastructural organization of recombinant Marburg virus nucleoprotein: comparison with Marburg virus inclusions. (3/182)
HeLa cells expressing the recombinant Marburg virus (MBGV) nucleoprotein (NP) have been studied by immunoelectron microscopy. It was found that MBGV NPs assembled into large aggregates which were in close association with membranes of the rough endoplasmic reticulum. Further analysis of these aggregates revealed that NPs formed tubule-like structures which were arranged in a hexagonal pattern. A similar pattern of preformed nucleocapsids was detected in intracellular inclusions induced by MBGV infection. Our data indicated that MBGV NP is able to form nucleocapsid-like structures in the absence of the authentic viral genome and other nucleocapsid-associated proteins. (+info)Distinct mechanisms of entry by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. (4/182)
Since the Marburg (MBG) and Ebola (EBO) viruses have sequence homology and cause similar diseases, we hypothesized that they associate with target cells by similar mechanisms. Pseudotype viruses prepared with a luciferase-containing human immunodeficiency virus type 1 backbone and packaged by the MBG virus or the Zaire subtype EBO virus glycoproteins (GP) mediated infection of a comparable wide range of mammalian cell types, and both were inhibited by ammonium chloride. In contrast, they exhibited differential sensitivities to treatment of target cells with tunicamycin, endoglycosidase H, or protease (pronase). Therefore, while they exhibit certain functional similarities, the MBG and EBO virus GP interact with target cells by distinct processes. (+info)Crystal structure of the matrix protein VP40 from Ebola virus. (5/182)
Ebola virus maturation occurs at the plasma membrane of infected cells and involves the clustering of the viral matrix protein VP40 at the assembly site as well as its interaction with the lipid bilayer. Here we report the X-ray crystal structure of VP40 from Ebola virus at 2.0 A resolution. The crystal structure reveals that Ebola virus VP40 is topologically distinct from all other known viral matrix proteins, consisting of two domains with unique folds, connected by a flexible linker. The C-terminal domain, which is absolutely required for membrane binding, contains large hydrophobic patches that may be involved in the interaction with lipid bilayers. Likewise, a highly basic region is shared between the two domains. The crystal structure reveals how the molecule may be able to switch from a monomeric conformation to a hexameric form, as observed in vitro. Its implications for the assembly process are discussed. (+info)Differential induction of cellular detachment by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. (6/182)
Human infection by Marburg (MBG) or Ebola (EBO) virus is associated with fatal haemorrhagic fevers. While these filoviruses may both incite disease as a result of explosive virus replication, we hypothesized that expression of individual viral gene products, such as the envelope glycoprotein (GP), may directly alter target cells and contribute to pathogenesis. We found that expression of EBO GP in 293T cells caused significant levels of cellular detachment in the absence of cell death or virus replication. This detachment was induced most potently by membrane-bound EBO GP, rather than the shed glycoprotein products (sGP or GP1), and was largely attributable to a domain within the extracellular region of GP2. Furthermore, detachment was blocked by the Ser/Thr kinase inhibitor 2-aminopurine, suggesting the importance of a phosphorylation-dependent signalling cascade in inducing detachment. Since MBG GP did not induce similar cellular detachment, MBG and EBO GP interact with target cells by distinct processes to elicit cellular dysregulation. (+info)Enzyme-linked immunosorbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins. (7/182)
The full-length nucleoprotein (NP) of Ebola virus (EBO) was expressed as a His-tagged recombinant protein (His-EBO-NP) by a baculovirus system. Carboxy-terminal halves of NPs of EBO and Marburg virus (MBG) were expressed as glutathione S-transferase-tagged recombinant proteins in an Escherichia coli system. The antigenic regions on the NPs of EBO and MBG were determined by both Western blotting and enzyme-linked immunosorbent assay (ELISA) to be located on the C-terminal halves. The C-terminal 110 and 102 amino acids of the NPs of EBO and MBG, respectively, possess strong antigenicity. The full-length NP of EBO was strongly expressed in insect cells upon infection with the recombinant baculovirus, while expression of the full-length NP of MBG was weak. We developed an immunoglobulin G (IgG) ELISA using His-EBO-NP and the C-terminal halves of the NPs of EBO and MBG as antigens. We evaluated the IgG ELISA for the ability to detect IgG antibodies to EBO and MBG, using human sera collected from EBO and MBG patients. The IgG ELISA with the recombinant NPs showed high sensitivity and specificity in detecting EBO and MBG antibodies. The results indicate that ELISA systems prepared with the recombinant NPs of EBO and MBG are valuable tools for the diagnosis of EBO and MBG infections and for seroepidemiological field studies. (+info)Sorting of Marburg virus surface protein and virus release take place at opposite surfaces of infected polarized epithelial cells. (8/182)
Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of Marburg virus in polarized epithelial cells. To this end, we established an MDCKII cell line that was able to express GP permanently (MDCK-GP). The functional integrity of GP expressed in these cells was analyzed using vesicular stomatitis virus pseudotypes. Further experiments revealed that GP is transported in MDCK-GP cells mainly to the apical membrane and is released exclusively into the culture medium facing the apical membrane. When MDCKII cells were infected with Marburg virus, the majority of GP was also transported to the apical membrane, suggesting that the protein contains an autonomous apical transport signal. Release of infectious progeny virions, however, took place exclusively at the basolateral membrane of the cells. Thus, vectorial budding of Marburg virus is presumably determined by factors other than the surface protein. (+info)According to the World Health Organization (WHO), Marburgviruses are toxiviral hemorrhagic fever-causing agents that belong to the Filoviridae family, which also includes Ebolaviruses. These enveloped, non-segmented, negative-stranded RNA viruses cause a severe and often fatal illness in humans and non-human primates. The Marburg virus was initially discovered in 1967, after simultaneous outbreaks occurred in laboratories in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia (now Serbia).
The virions of Marburgviruses are typically filamentous or U-shaped and measure approximately 80 nm in diameter. The genome consists of a single non-segmented, negative-sense RNA molecule that encodes seven structural proteins: nucleoprotein (NP), polymerase cofactor protein (VP35), matrix protein (VP40), glycoprotein (GP), transcription activator protein (VP30), RNA-dependent RNA polymerase (L), and a small hydrophobic protein (sVP24 or VP80).
Marburgviruses are primarily transmitted to humans through contact with the bodily fluids of infected animals, such as bats and non-human primates. Human-to-human transmission can occur via direct contact with infected individuals' blood, secretions, organs, or other bodily fluids, as well as through contaminated surfaces and materials.
The incubation period for Marburg virus disease (MVD) typically ranges from 2 to 21 days. Initial symptoms include fever, chills, headache, muscle aches, and general malaise. As the disease progresses, patients may develop severe watery diarrhea, abdominal pain, nausea, vomiting, and unexplained bleeding or bruising. In fatal cases, MVD can cause multi-organ failure, shock, and death, often within 7 to 14 days after symptom onset.
Currently, there are no approved vaccines or antiviral treatments specifically for Marburg virus infections. However, supportive care, such as fluid replacement, electrolyte management, and treatment of secondary infections, can help improve outcomes for MVD patients. Preventive measures, including the use of personal protective equipment (PPE) and proper infection control practices, are crucial to reducing the risk of transmission during outbreaks.
Marburg Virus Disease (MVD) is an acute and often fatal viral hemorrhagic fever illness caused by the Marburg virus, a member of the filovirus family. It's a highly infectious disease that can be transmitted from human to human through direct contact with infected bodily fluids, tissues, or indirectly through contaminated surfaces and materials.
The incubation period for MVD ranges from 2 to 21 days, after which symptoms such as fever, chills, headache, muscle aches, severe malaise, and progressive weakness appear. Around the fifth day of illness, a maculopapular rash may occur, followed by diarrhea, nausea, vomiting, abdominal pain, and non-bloody stools. In some cases, patients may develop severe bleeding disorders, shock, liver failure, and multi-organ dysfunction, which can lead to death in 24-48 hours.
Currently, there are no approved vaccines or antiviral treatments for MVD, but supportive care is crucial for managing the symptoms of the disease. Preventive measures such as avoiding contact with infected individuals and their bodily fluids, wearing protective clothing, and practicing good hygiene can help prevent the spread of the virus.
Filoviridae is a family of negative-sense, single-stranded RNA viruses that includes three genera: Ebolavirus, Marburgvirus, and Cuevavirus. These viruses are known to cause severe hemorrhagic fever in humans and nonhuman primates, with high fatality rates. The most well-known members of this family are Ebola virus and Marburg virus.
The virions of Filoviridae are filamentous, often having a "U," "6," or "hook" shape, and can be up to 14,000 nanometers in length. The genome of these viruses is non-segmented and contains seven genes that encode for structural proteins and enzymes necessary for replication.
Transmission of Filoviridae occurs through direct contact with infected bodily fluids or contaminated surfaces, and infection can result in a range of symptoms including fever, severe headache, muscle pain, weakness, fatigue, and hemorrhage. There are currently no approved vaccines or antiviral treatments for Filoviridae infections, although several are in development.
Ebolavirus is a genus of viruses in the family Filoviridae, order Mononegavirales. It is named after the Ebola River in the Democratic Republic of Congo (formerly Zaire), where the virus was first identified in 1976. There are six species of Ebolavirus, four of which are known to cause disease in humans: Zaire ebolavirus, Sudan ebolavirus, Bundibugyo ebolavirus, and Tai Forest ebolavirus (formerly Cote d'Ivoire ebolavirus). The fifth species, Reston ebolavirus, is known to cause disease in non-human primates and pigs, but not in humans. The sixth and most recently identified species, Bombali ebolavirus, has not been associated with any human or animal diseases.
Ebolaviruses are enveloped, negative-sense, single-stranded RNA viruses that cause a severe and often fatal hemorrhagic fever in humans and non-human primates. The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission. Fruit bats of the Pteropodidae family are considered to be the natural host of Ebolavirus.
The symptoms of Ebolavirus disease (EVD) typically include fever, severe headache, muscle pain, weakness, fatigue, and sore throat, followed by vomiting, diarrhea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding. The case fatality rate of EVD is variable but has been historically high, ranging from 25% to 90% in past outbreaks depending on the species and the quality of medical care. There are no licensed specific treatments or vaccines available for EVD, although several promising candidates are currently under development.
Ebola Hemorrhagic Fever (EHF) is a severe, often fatal illness in humans. It is one of the five identified subtypes of the Ebolavirus. The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.
The early symptoms include sudden onset of fever, fatigue, muscle pain, headache and sore throat. This is followed by vomiting, diarrhea, rash, symptoms of impaired kidney and liver function, and in some cases, both internal and external bleeding.
Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes.
The virus is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as fruit bats, porcupines and non-human primates. Then it spreads in communities through human-to-human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials contaminated with these fluids.
Healthcare workers have frequently been infected while treating patients with suspected or confirmed EVD due to a lack of adequate infection prevention and control measures.
There are currently no approved specific antiviral drugs or vaccines for Ebola. Several promising treatments and vaccine candidates are being evaluated.