Virology They contain single-strand, non-infectious RNA genomes. Ebolavirus genomes are approximately 19 kilobase pairs long and contain seven genes in the order 3-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5-UTR.The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV, and TAFV) differ in sequence and the number and location of gene overlaps. Like all filoviruses, ebolavirions are filamentous particles that may appear in the shape of a shepherds crook or in the shape of a U or a 6, and they may be coiled, toroid, or branched. In general, ebolavirions are 80 nm in width, but vary somewhat in length. In general, the median particle length of ebolaviruses ranges from 974 to 1,086 nm (in contrast to marburgvirions, whose median particle length was measured at 795–828 nm), but particles as long as 14,000 nm have been detected in tissue culture. Their 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. Ebolavirus structural glycoprotein (known as GP1,2) is responsible for the virus ability to bind to and infect targeted cells.The viral RNA polymerase, encoded by the L gene, partially uncoats the nucleocapsid and transcribes the genes into positive-strand mRNAs, which are then translated into structural and nonstructural proteins. 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-strand antigenomes that are, in turn, transcribed into negative-strand virus progeny genome copy. 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. The Ebola virus genetics are difficult to study due to its virulent nature Pathophysiology Cells lining the inside of blood vessels (endothelial cells), macrophages, monocytes, and liver cells are the main targets of infection. After infection, a secreted glycoprotein, known as small soluble glycoprotein (sGP) or as the Ebola virus glycoprotein (GP), is synthesized. Ebolavirus replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms a trimeric complex, which binds the virus to the endothelial cells. The sGP forms a dimeric protein that interferes with the signaling of neutrophils, a type of white blood cell, which allows the virus to evade the immune system by inhibiting early steps of neutrophil activation. These white blood cells also serve as carriers to transport the virus throughout the entire body to places such as the lymph nodes, liver, lungs, and spleen. The presence of viral particles and cell damage resulting from viruses budding out of the cell causes the release of chemical signals (such as TNF-α, IL-6, and IL-8), which are molecular signals for fever and inflammation. The damage to human cells, caused by infection of the endothelial cells, decreases blood vessel integrity. This loss of vascular integrity is furthered with the synthesis of GP, which reduces specific integrins responsible for cell adhesion to the intercellular structure, and damage to the liver, which leads to improper clotting. Filoviral infection is also known to interfere with proper functioning of the innate immune system. Ebolavirus proteins have demonstrated the ability to blunt the human immune systems response to viral infections by interfering with cells ability to produce and respond to interferon proteins such as interferon-alpha, interferon-beta, and interferon gamma. This interference is accomplished by the VP24 and VP35 ebolavirus structural proteins. When cells are infected with ebolavirus, receptors located in the cells cytosol (such as RIG-I and MDA5) or outside of the cytosol (such as Toll-like receptor 3, Toll-like receptor 7, Toll-like receptor 8, and Toll-like receptor 9), recognize infectious molecules associated with the virus. After these receptors are activated, proteins including interferon regulatory factor 3 and interferon regulatory factor 7 start a signaling cascade that leads to the expression of type 1 interferons. Type 1 interferons are then released and bind to neighboring uninfected cells expressing the IFNAR1 and IFNAR2 receptors on their surface. Once interferon has bound to its receptors on the neighboring uninfected cell, the signaling proteins STAT1 and STAT2 are activated and move to the uninfected cells nucleus. This triggers the expression of interferon-stimulated genes, which code for proteins that have antiviral properties. Ebolavirus V24 protein prevents the STAT1 signaling protein in the neighboring uninfected cells from entering the cells nucleus and therefore prevents the creation of these antiviral proteins. A separate ebolavirus protein, known as VP35, directly inhibits the production of interferon-beta. croxxmore croxxmoremed Ebola virus disease Croxxmore Medical Device China : - Sourcing and Manufacturing Solution - Supplier Inspection/ QC - In-Country Representation - Medical Device OEM/ODM/OBL - China Medical Device Industry Advisory - Marketing Analysis and Research in China - Medical Distributor Search in China - Exhibition Service - Medical Supplies - China Medical Device Registration - China Medical Device OEM - China Medical Device Outsourcing - China Medical Device Sourcing - China Medical Device Local Agents - China Drug Registration - China Cosmetic Registration - China Medical Device Manufacturing Solution
Posted on: Sat, 18 Oct 2014 11:15:01 +0000
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