The Reproduction strategy of the Dengue Virus Essay
The first two stairss in a viral life rhythm involve fond regard and entry. The scope of host and tissue tropism is straight dependent on the first two stairss listed supra. It has been determined that there exists a great tissue tropism for dandy fever virus due to the possible presence of several cellular receptors. The viral receptor that has been identified for primary dandy fever virus infection is the E glycoprotein. This protein plays a critical function in commanding infection every bit good as tropism. Controversial theories exist nevertheless on the cellular receptor for fond regard of dandy fever virus. Since dandy fever virus has been shown to retroflex successfully in a broad assortment of cell civilizations obtained from mammalian and arthropod tissues, it may be possible that there may be different receptors based on the type of host cell infected. Two glycoproteins have been reported as receptors for dandy fever – 4 infections. Besides, two tubulin like proteins were identified as receptors for dandy fever virus 2 infections. Furthermore, a laminin – binding protein was established to be a common receptor for dandy fever – 3 and dengue – 4 viruses. Several different proteins receptors have been identified for different types of mammalian cells such as monocytes, macrophages, dendritic cells, B and T lymph cells, endothelial cells, and bone marrow. These receptors may include heat daze proteins, laminin receptor, mannose receptor, CD – 14 associated protein, and DC – SIGN ( 1 ) . Some research workers have shown that Lipo-Hepin sulphate was involved in the fond regard of dandy fever virus cells. This receptor is normally present on cells and serves as an initial receptor for many pathogens. The Lipo-Hepin sulphate receptor is specific to the extremely sulfated signifier of the receptor. With the digest of all of the above information is has been hypothesized that dandy fever E glycoprotein reacts with two possible marks on the cell ( 2 ) . The first receptor may be the omnipresent, low affinity heparan sulphate or DC – Sign receptors that help roll up the viral atoms. The 2nd receptor would so be a higher affinity one that would assist with the physical entry of the viral atom. Variations are present in the E – glycoprotein based on the serotype of the virus and this fluctuation will besides act upon viral interaction with the cells that get infected ( 1 ) .
There are four good defined paths of entry that dengue virus may utilize. These include phagocytosis, macropinocytosis, clathrin – mediated endocytosis, and caveolae – mediated endocytosis. Some of the non so good characterized methods of entry include lipid raft – mediated endocytosis dependant on dynamin, lipid raft – mediated pathway independent of dynamin, and nonclathirin noncaveolar – mediated tract which is independent of lipid tonss. Harmonizing to some early surveies the path of entry was chiefly merger at physiological pH, but now it has been determined that the path of entry for infection is receptor – mediated endocytosis at low pH. Membrane merger occurs in endosomal compartments and the low pH conditions of these endosomes cause the viral E – glycoprotein to undergo a conformational alteration. This exposes the merger domains that were antecedently hidden and initiates the membrane merger procedure which releases viral RNA into the cytol. Another group of research workers have late demonstrated that dandy fever virus 2 enters via the clathirin dependent endocytosis path in mosquitoes every bit good as HeLa cells. Another path of entry that was shown for mosquitoes was independent of lipid raft unity Thus a assortment of consequences were obtained for paths of entry for dandy fever virus which prompts that dandy fever virus may use several different paths of entry ( 1 ) .
Once endocytosis has occurred and the virus has entered the cell, uncoating occurs via merger of the envelope to the endosomal membrane. As discussed above, the low pH of the endosome causes a conformational alteration in the E glycoprotein which causes the exposure of the merger sphere that controls the merger of the viral envelope. Dengue virus RNA is positive stranded that is structured like cellular messenger RNA. It possesses a 5 ‘ guanosine cap construction, a 5’untranslated part ( UTR ) , one unfastened reading frame, and a 3 ‘ UTR. The anomalousness is that it lacks a polyadenylated tail. Due to the deficiency of Poly A tail dandy fever can non utilize the same machinery that cellular messenger RNA utilizations. Therefore, dengue utilizations schemes such as the virus undergoes interlingual rendition when cellular interlingual rendition has been inhibited due to a coinfection with another virus, or under conditions with high osmolarity, or due to the repression of of import induction factors. Adaptation to the host may be the ground that dandy fever virus obtained this ability to interpret under a assortment of different conditions. Cellular tropism of the virus can be determined by the efficaciousness of the initial interlingual rendition. It was demonstrated by a survey conducted on different strains of dandy fever virus that the 3 ‘ UTR may be involved in ordinance of interlingual rendition. This part in partnership with the 5’UTR has been shown to possess belongingss that are similar to the poly A tail in advancing interlingual rendition. After the readying of translational machinery, the initial codon has to be spotted by the little ribosomal unit in order to get down elongation. A hair pin construction downstream of the dandy fever virus – 2 start codon has been shown to assist with sweetening of interlingual rendition based upon its stableness ( 3 ) .
Dengue virus utilizes the same positive strand for both interlingual rendition and reproduction. These two procedures occur at different times. After the interlingual rendition of the initial strand, the viral atom produces vRNA. This involves a negative strand RNA that can be used in the hereafter for the production of more positive strands. Even though this is non good understood, it has been shown that the positive strand DNA is produced in surplus by the virus. The 3’UTR discussed above that helped modulate interlingual rendition besides plays a function in the ordinance of vRNA synthesis ( 3 ) .
The synthesized RNA is packaged into a mirid bug by the C protein. Inside the lms of the ER the prM and the E protein East in an appropriate place. Then the prM and the E proteins associate with each other to organize a curving surface construction. Since there no interactions spotted with C and prM, it may be assumed that is procedure is random. The assembled viral atom shows 60 spike projections that have formed by the heterodimeric associations between prM and E. This immature atom usually forms in the endoplasmic Reticulum and ripening takes topographic point as the viral atom goes through the secretory tract. The low pH conditions of the trans- Golgi web cause a dissociation between the prM and E protein and the merger protein E is capped by the prM. This leads to the formation of dimers that tend to put level on the surface of the viral atom. The formation of this construction is what enables the furin ( a cellular endoprotease ) to split off the prM cap. Furin besides caused the interrupting apart of prM to for membrane associated peptides M and Pr. These peptides have been shown to function as chaperones for the E protein while it ‘s going through the secretory tract. They prevent any conformational alteration in the E protein that could take to membrane merger. Once the Pr peptide dissociates, mature viral atom formation occurs. Mature particles so egress through the cell through exocytosis ( 4 ) .