Dr Ashok Chauhan

Dr. Chauhan specializes in molecular virology and his research focuses on understanding viral replication and neuropathogenesis of RNA viruses including retroviruses such as HIV. The HIV is a retrovirus having RNA and DNA phases in viral life cycle. Virus is enveloped and diploid of ~9.2 kb genome in size. The HIV enters into the host cells through receptor which is CD4 and co-receptor either CCR5 or CXCR4 or sometimes minor co-receptors. The HIV produces persistent infection upon integration of viral genome with the host chromosome on compromising host innate immune system. In humans, HIV is neuroinvasive and produces brain infection which leads to cognitive impairment, motor dysfunction and finally severe form of disease known as HIV associated dementia in 15-20 percent of untreated HIV infected cases. My lab is specifically interested in HIV-1 replication in PBMCs and neuro-glial cells particularly viral-persistence and low level of viral transcription in brain and its impact on dysregulation of astrocytes and neuronal functions through inflammatory molecules. Viruses in general evade host’s innate defense system for establishment, therefore, association with cellular gene expression in HIV infection and early viral gene products (Tat and Rev) are the focus of my research using cutting edge technology such as gene array and proteomics and RNAi/miRNA. The HIV regulatory proteins Tat and Rev are the earliest proteins in HIV life cycle and control the whole HIV replication. Blocking either of them-- in particular Tat, shuts down all the HIV mRNA transcripts synthesis and subsequently cripple HIV replication. Using microarray and protein array we have picked up cellular genes dysregulated by HIV-Tat protein and further exploring their functions in relation to neuronal apoptosis and impairment of innate immune system genes in astrocytes and PBMCs. My laboratory has developed various expression vectors and transgenic cells to study HIV in in-vitro cell systems. We have observed that Tat protein localizes permanently in the nucleus and nucleolus and therefore, is implicated in cellular gene regulation apart from HIV transcription. Further, viral replication is a complex process wherein viral components are regulated temporally and comes in viral life cycle at a certain time and set the stage for another viral component to play a` role in further step. Understanding each step in viral replication will help in designing rational vaccines and therapeutic inhibitors.
Second interest is hepatitis C virus (HCV) and encephalopathy. The HCV is an RNA virus, which produces chronic infection in humans and leads to acute hepatitis, cirrhosis, hepatic cellular carcinoma and hepatic encephalopathy. The exact mechanism of encephalopathy is not yet known. We are investigating extra hepatic cell population as a target of HCV in relation to neuropathogenesis in particular astrocytes which are brain resident cells expressing HCV receptor CD81
Third interest is gene transfer and siRNA delivery to brain and PBMCs in-vitro and in-vivo using cell penetrating peptides (CPPs) in combination with siRNA and viral vector DNA such as lentiviral, adenoviral and AAV vectors. The major impediment in gene delivery to brain is blood brain barrier (BBB) and we are exploring chimeric combinations of different peptides in particular RNA binding domain of HIV Tat protein with cell penetrating domains for siRNA delivery

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