Our area of interest is to understand: a) The adverse effects of human pharmaceuticals on the immune system in-vivo and in-vitro in terms of suppression/enhancement of immune response and understanding the underlying molecular mechanism. b) The inhibitory activity of synthetic compounds or natural products against HIV-1-Reverse Transcriptase (RT) enzyme of NNRTI class. c) The role of   HIV-1 Nef  and host protein interactions that are regulating pathways which are responsible for viral survival and maintenance in host.. We are targeting these interactions as potential target to develop new inhibitors which could be useful to understand the effect of these interactions in HIV-1 progression.
            HIV-1 Nef modulates several functions through interaction with over 30 host proteins. The structure-function relationship was depicted by solving the Nef crystal structure. The dimmer tetramer transition showed that N-terminal region of Nef was sterically occuled and the distal C-terminal loop was accessible in tetramer state. The inaccessible and accessible regions of Nef suggest the selective interaction with host proteins. The tetramer associates through C4 symmetry instead of the 222 symmetry.

Fig 1. The full-length HIV-1 Nef forms a tetramer with a 4-fold symmetry (bottom right). This dimer to tetramer transition involves an association that exhibits 222 symmetry have large changes to the relative spatial disposition of the subunits of the dimer.

            We used C. elegans to study the HIV-1 Nef pathogenesis.  HIV-1 Nef protein was transcellularly introduced into worms. We observed a marked lipodystrophy, effect on neuromuscular function, impaired fertility and reduced longevity in the worms exposed to Nef. The observed effects resemble to those observed in Nef transgenic mice and most interestingly the effects also relate to some of the pathogenic aspects exhibited by human AIDS patients. This in vivo model could be used for studying the interactions of Nef with host proteins and further could be used for identifying possible inhibitors of such interactions.

Figure 2. A representative phase contrast image of live worms showing normal (a) and thin Nef treated nematodes (b) on day8 of treatment. Scale bar, 100 mm. Fig. 2c is the graphical representation of the ‘total body area’ of nematodes. Figure 3. Representative images for Nile red staining of Control (a, b) and Nef treated (c, d) worms (on day 8 of treatment) showing the reduced amount of lipid deposits in Nef treated worms as compared to Control. (a) and (c) are fluorescence images, (b) and (d) are merged images from DIC and fluorescent microscopy. Scale bar, 50 mm. Fig. 3e is graphical representation for fluorescence intensity of the nematodes as quantified using Image J software.

HIV-1 isolatete , from India nef protein (nef) gene, Complete cds. Accession No. GQ184335, GQ184336, GQ184337, GQ184338, GQ184339, GQ184340, and GQ184341, Gupta,S., Singh,P., Tripathi,A.K., Ramachandran, R. and Tripathi,R.K., 2009.