Q2. What are the future works in this paper?
The presence of both NS1 and the antibodies it induces during the acute phase of disease is unusual and further studies are required to determine the modulating effect each has on the other, and of course the contribution of their interaction, immune complexes, to the overall disease process. Their hope is that it will provide insights into further research directions that may answer some of the many outstanding questions posed above. Perhaps one of the most intriguing aspects of this viral gene product can be found in a comparison with the genome coding strategy of the two related members of the Flaviviridae family, the hepaciviruses and pestiviruses. Studies that directly compare the replication of these separate members of the Flaviviradae may be quite revealing.
Q3. What is the role of NS1 in the replication of dengue virus?
Intracellular NS1 plays an essential cofactor role in virus replication and has been shown to co-localize with dsRNA and other components of viral replication complexes (Mackenzie et al., 1996; Westaway et al., 1997).
Q4. how many amino acids are required to mediate a cleavage?
In a recombinant vaccinia virus expression system it was found that 70% of NS2A was required to mediate effective cleavage (Hori and Lai, 1990; Leblois and Young, 1995).
Q5. What is the role of NS1 in the development of dengue?
At a time of rising anti-NS1 antibody levels and the presence of NS1 in immune complexes (IC), IC deposition and complement activation is more likely to contribute to severe disease outcome, at least for dengue, than is free NS1 binding to complement regulating proteins.
Q6. What is the NS1 complicating factor for detection in secondary dengue infections?
However a complicating factor for NS1 detection in secondary dengue infections is the rapid anamnestic rise of serotype cross-reactive anti-NS1 antibodies.
Q7. What is the role of NS1 in the immune response?
In addition to complement-dependent and independent antibody mediated protection, NS1 has also been identified as a target of cell-mediated immunity, indicating that both arms of the immune response are likely to play a role (Gao et al., 2008; Green and Rothman, 2006; MuraliKrishna et al., 1995).
Q8. What is the role of NS1 in dengue?
One of the major concerns for any vaccine strategy against the dengue viruses is the potential priming of antibody dependent enhancement (ADE), an important and accepted risk factor for the development of the more severe disease outcomes of dengue infection, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS).
Q9. what is the role of sns1 in the pathogenesis of flavivirus?
NS1 induction of autoantibodies and a potential role in pathogenesisDespite the fact that most antibodies directed against NS1 have been found to provide some level of passive protection to mice from a lethal flavivirus challenge (Henchal et al., 1988 Schlesinger, 1985 #233; Schlesinger et al., 1986), a small number have been shown to increase morbidity (Falconar,1997, 2008; Henchal et al., 1988).
Q10. What is the role of sNS1 in the formation of soluble membrane attack complexe?
deposition of the sNS1-C4BP complex on to the cell surface could lead to inactivation of cell surface bound C4b thereby protecting infected cells from complement mediated lysis (Avirutnan et al., 2011) (Figure 4, step 14).
Q11. What is the role of NS1 in the development of antiviral drugs?
The importance of correct NS1 glycosylation for virus replicative capacity and the potential of this post-translational modification as a target for antiviral drug design was recently demonstrated in a study of the effects of the α-glucosidase inhibitor, Celgosivir (Rathore et al., 2011).
Q12. What is the role of the amino acid substitution in the dimerization process?
In Kunjin virus and MVE, a single amino acid substitution at residue 250 from proline to leucine has been shown to result in a loss of detectable dimers, suggesting a role for this C-terminal region of the protein in the dimerization process (Figure 3A).
Q13. What is the role of NS1 in the formation of soluble membrane attack complexes?
Further evidence for NS1 involvement in the generation of soluble membrane attack complexes was suggested when NS1 was found to bind directly to the complement inhibitory factor clusterin, which inhibits the formation of the membrane attack complex (Kurosu et al., 2007).
Q14. What is the role of NS1 in the pathogenesis of dengue?
This immune-mediated liver injury in mice provides supporting evidence that anti-NS1 antibody responses may also play a role in the liver damage characteristically seen in human dengue virus disease.
Q15. What is the role of NS1 in dengue vaccines?
Although overtaken to some degree by live attenuated chimeric virus vaccine candidates, there is renewed interest in NS1 as a component of second generation sub-unit vaccines for dengue as well as other flaviviruses (Krishna et al., 2009; Miller, 2010).