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In this study, we used the GP gene to investigate the mechanism by which EBOV induces cytotoxicity. GP overexpression inhibited the expression of cell surface proteins, cellular adhesion molecules, and immune surveillance proteins in HEK293T cells. GP cytotoxicity was dependent on its highly glycosylated, mucin-like domain. However, the precise role of GP cytotoxicity in EBOV pathogenesis remains unclear.
The GP of EBOV is the major site of fusion between the virus and the target cell, where it causes infection. The GP has several essential roles in the EBOV life cycle, including attachment to target cells and entry into target cells. GP expression in the cells of different species of EBOV is important for determining the virion’s pathogenic capacity. For instance, adenovirus-expressed ZEBOV GP induces endothelial cell damage in human vessel explants, while REBOV GP is only cytotoxic to monkey vessels. Furthermore, the GP of ZEBOV and REBOV differ in their susceptibility to furin cleavage and the amino acid sequence of the TACE cleavage site.
EBOV GP binding site residues
A series of studies conducted on GP binding site residues of EBOV have provided an understanding of how this virus binds to its receptor. Using a series of representative glycoproteins, we identified conserved residues within the GP1 binding site. The conserved residues form at least five contiguous regions and are at least four amino acids long. However, the role of GP cytotoxicity in EBOV pathogenesis remains unclear.
The GP1 binding site contains several regions that are thought to be involved in fusion-mediated conformational changes. Residues 55-201 of GP1 are located near the disulfide bond, and residues Phe159, Tyr162, and Ile170 are located in the GP1 core. Moreover, residues Phe88 and Gly88 are located close to the hydrophobic fusion loop and may affect its structural integrity.
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Indus Valley Civilization
The Indus Valley Civilization was an ancient civilization that flourished in the Indus Valley of India. Several major sites are associated with the civilization, including Harappa, a city surrounded by massive brick walls. Another site is the Kot Diji culture, which is noted for its well-made pottery and houses built with stone foundations. The oldest civilization of the Indus Valley Civilization, Mehrgarh, was a pioneer and the first city of this civilization. The inhabitants of the city lived in mud-brick houses and learned to create pottery around 6,000 B.C.
The most significant sites of the Indus Valley Civilization are Harappa, Mohenjo-Daro, and Dholavira. These sites were inhabited at least 5 centuries ago and are located in the region of Rajasthan. Many of these sites have been excavated. The bricks, which were made of earth, were not water-tight and there was no drainage system.
Oklahoma’s Multnomah Falls
The Multnomah Falls lodge is a great place to stay for a visit to the waterfall. The property has ample parking, a great restaurant, and great views of the falls. The parking lot can be crowded on weekends during tourist season. However, it is still worth visiting regardless of the time of year. In the winter, the falls are covered with ice, making them an especially beautiful sight.
To visit the falls, hikers can take the Benson Footbridge, a 45-foot-long bridge that spans the lower cascade. From there, they can descend by a series of 11 switchbacks to reach the observation deck. The observation deck provides spectacular views of the Columbia Gorge and Little Multnomah.