Title: Development of novel Anti-Hiv-1 Therapy: accessory protein nef as target
Raj Kamal Tripathi has completed his PhD at the age of 27 years from Kanpur University and postdoctoral studies from Centre d' Immunologie (CIML), Marseille, France and Dept. of Immunology, Duke University Medical Centre, Durham, USA. He is a Principal Scientist in CSIR-CDRI, Lucknow, India, a premier drug development Institute. He has received national and International awards during his research career. He has published more than 25 papers in reputed journals and has one US patent.
HIV-1 is a retrovirus which when integrates with the human genome, establishes functional disease. The viral replication in the host T cell destroys the immune system, creating a pathological condition and rendering the host vulnerable to secondary infection, thus leading to mortality. The present anti-HIV-1 therapy is largely based on the inhibitory functions of the viral proteins which are crucial for the viral life cycle. There are some accessory proteins too, which may not be as essential for the viral life cycle, but may be critical in the survival of the virus in the host. Deletion of Nef, an accessory protein which does not have any enzymatic activity, favours the hypothesis that Nef- host protein interaction leads to the progression of AIDS in human and monkey. The insertion of Nef gene in mice and trans-cellular introduction of Nef protein in C.elegans leads to the exhibition of AIDS like symptoms in them.
Our laboratory is interested in identifying novel host cellular proteins that interact with Nef and decipher the cellular pathways regulated by it. We observe these interactions as potential targets for antiretroviral therapy. We have identified two Nef inhibitors that impede Nef-ASK-1 and Nef-GCC185 interaction regulating apoptosis and immune evasion respectively in the Nef infected cells. Based on our results, we propose the idea that these inhibitors may clear the viral infected cells from the host.