Dhf Disease Pathology

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  • Topic: Dengue fever, Aedes, Aedes aegypti
  • Pages : 6 (1814 words )
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  • Published : March 23, 2011
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Defn:Dengue Haemorrhagic Fever(DHF) are acute febrile diseases transmitted by mosquitoes, which occur in the tropics, can be life-threatening, and are caused by four closely related virus serotypes of the genus Flavivirus, family Flaviviridae.It was identified and named in 1779. It is also known as breakbone fever, since it can be extremely painful. Causative Agent: . Dengue is transmitted to humans by the Aedes (Stegomyia) aegypti or more rarely the Aedes albopictus mosquito. The mosquitoes that spread dengue usually bite at dusk and dawn but may bite at any time during the day, especially indoors, in shady areas, or when the weather is cloudy.

Virology: Dengue fever is caused by Dengue virus (DENV), a mosquito-borne flavivirus. DENV is an ssRNA positive-strand virus of the family Flaviviridae; genus Flavivirus. There are four serotypes of DENV. viral serotypes: dengue virus 1 (DENV-1), dengue virus 2 (DENV-2), dengue virus 3 (DENV-3), and dengue virus 4 (DENV-4). Genetic studies of sylvatic strains suggest that the 4 viruses evolved from a common ancestor in primate populations approximately 1000 years ago and that all 4 viruses separately emerged into a human urban transmission cycle 500 years ago in either Asia or Africa.1,8 Albert Sabin speciated these viruses in 1944.

The virus has a genome of about 11000 bases that codes for three structural proteins, C, prM, E; seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5; and short non-coding regions on both the 5' and 3' ends. E protein The envelope protein, found on the viral surface, is important in the initial attachment of the viral particle to the host cell. Several molecules which interact with the viral E protein (ICAM3-grabbing non-integrin., CD209 ,Rab 5 , GRP 78 ,and The Mannose Receptor )have been shown to be important factors mediating attachment and viral entry. prM/M protein

The membrane protein, which is important in the formation and maturation of the viral particle, consists of seven antiparallel β-strands stabilized by three disulphide bonds. The glycoprotein shell of the mature DENV virion consists of 180 copies each of the E protein and M protein. The immature virion starts out with the E and prM proteins forming 90 heterodimers that give a spiky exterior to the viral particle. This immature viral particle buds into the endoplasmic reticulum and eventually travels via the secretory pathway to the golgi apparatus. As the virion passes through the trans-Golgi Network (TGN) it is exposed to low pH. This acidic environment causes a conformational change in the E protein which disassociates it from the prM protein and causes it to form E homodimers. These homodimers lay flat against the viral surface giving the maturing virion a smooth appearance. During this maturation pr peptide is cleaved from the M peptide by the host protease, furin. The M protein then acts as a transmembrane protein under the E-protein shell of the mature virion. The pr peptide stays associated with the E protein until the viral particle is released into the extracellular environment. This pr peptide acts like a cap, covering the hydrophobic fusion loop of the E protein until the viral particle has exited the cell. NS3 protein

The DENV NS3 is a serine protease, as well as an RNA helicase and RTPase/NTPase. The protease domain consists of six β-strands arranged into two β-barrels formed by residues 1-180 of the protein. The catalytic triad (His-51, Asp-75 and Ser-135), is found between these two β-barrels, and its activity is dependent on the presence of the NS2B cofactor. This cofactor wraps around the NS3 protease domain and becomes part of the active site. The remaining NS3 residues (180-618), form the three subdomains of the DENV helicase. A six-stranded parallel β-sheet surrounded by four α-helices make up subdomains I and II, and subdomain III is composed of 4 α-helices surrounded by three shorter α-helices and two antiparallel β-strands. NS5 protein

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