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Molecular Virology » Research |
| Molecular Virology |
Current Research Interests
In a factory, someone has to stand on the loading dock, checking the goods going out. By recognizing labels like bar codes on each shipment, the loading dock su pervisor makes sure that the products get where they are supposed to go. A cell is like a factory: one of its most important jobs is to produce proteins, like t ranscription factors and nuclear transport receptors. But in cellular factories, the sorting task is complicated by the fact that proteins are used by the cell itself as well as delivered to outside "customers". Scientists are succeeding at deciphering the cell's complex bar-coding system. But, surprisingly, they have never managed to get at the loading dock itself to see how HIV PICs are actually shipped to their destinations. |
Projects
Mechanism of human immunodeficiency virus (HIV) genome nuclear transport:
Regulation of HIV-1 infectivity and pathogenesis of AIDS remain central interests of the laboratory. Unlike the typical animal-oncoretroviruses, lentiviruses such as HIV have the ability to infect and replicate within non-cycling cells. Nucleo-cytoplasmic transport of the viral genome is vital for the replication and assembly of many viruses. Nuclear transport of Human immunodeficiency viral (HIV) genome, for instance, is critical for productive infection in non-dividing cells such as human macrophages. Our understanding on the nuclear import of HIV preintegration complexes into the nucleus of non-dividing cells remains rudimentary, and identification of cellular protein(s) which interact with viral PICs is eagerly awaited and will reveal cellular system that are important to diverse and basic cellular processes. Our laboratory will focus on two issues: mechanism of HIV PICs nuclear import, and signals in PICs that regulate its nuclear import. To achieve this goal we will clone and characterize the host genes that are involved in this process. We will also attempt to identify how the host genes interact with viral proteins to bring about the events of HIV pathogenesis. Furthermore, a better understanding of nuclear transport during viral infection might prove useful for designing antiviral therapies and for designing delivery vectors for gene therapy, which is a rapidly developing and increasingly important area of research in biomedical sciences.
HIV and Host cell cycle regulation:
Unlike simple retroviruses, HIV encodes several accessory proteins which are packaged into the virus particles (Vpr of HIV-1; Vpr and Vpx of HIV-2) via interaction with Gag precursor polyprotein. In addition to its role in nuclear import, HIV-1 Vpr has a second, distinct activity in expressing cells, induction of arrest in the G2 phase of the cell cycle and increases HIV replication. The cells expressing Vpr contain very low levels of p34cdc2-cyclinB associated kinase activity, although both proteins are expressed. The activity of p34cdc2-cyclinB kinase is critical for the transition of from G2 to mitosis. Recently we identified a Vpr interacting cellular protein named hVIP (human Vpr interacting protein) using yeast two-hybrid trap system, which is an essential cofactor in p34cdc2-cyclinB complex. Vpr interact with hVIP and negatively regulates the kinase activity associated with p34cdc2-cyclinB complex suggesting that Vpr function likely to be an upstream regulator of the G2 to M transition. Our laboratory is examining the mechanism of Vpr and hVIP interaction on HIV pathogenesis and the role of hVIP in mammalian cell cycle. |
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| Contact Information |
| Email: |
maha<at>cdfd.org.in |
| Phone: |
+91-40-27151344-46-47-48 extn.1203
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| Fax: |
+91-40-27151344 |
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| Last updated on: 7th June, 2006. |
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