Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/5043
Title: Regulatory role of Mycobacterium tuberculosis PPE proteins on proinflammatory signaling pathway and activation of HIV-1 LTR
Researcher: Bhat, Khalid Hussain
Guide(s): Mukhopadhyay, Sangita
Keywords: Human Immunodeficiency Virus
DNA
TLR2
HIV-1 LTR
Coinfection
Mycobaterium tuberculosis
Rv0256c
Rv1168c
PE proteins
PPE proteins
Upload Date: 5-Nov-2012
University: Manipal University
Completed Date: 22/12/2011
Abstract: Opportunistic infections in human immunodeficiency virus (HIV) infected patients are often associated with an increase in HIV replication. Due to the high incidence of both HIV and Mycobacterium sp. infection in the developing countries, tuberculosis (TB) has emerged to be the most common opportunistic infection in HIV-infected patients world-wide. Co-infection with the bacilli has been postulated to be an important exogenous factor that influences the severity and rate of disease progression in HIV-infected individuals, reducing the chances of survival and increasing the risk of HIV transmission. Macrophages act as a host to both M. tuberculosis and HIV and hence appear to be a possible site of interaction for these two deadly pathogens. The incidence of HIV type 1 (HIV-1) infection is found to be accelerated in people infected with Mycobacterium tuberculosis. However, the mechanisms by which mycobacterial protein(s) enhance transcriptional activity of HIV-1 LTR, the sole promoter element of HIV (Bernier et al., 1998, Kitaura et al., 2001), is not clearly understood. In the present study it has been demonstrated that one of the M. tuberculosis PPE proteins, Rv1168c can trans-activate HIV-1 LTR in monocyte/macrophage cells by targeting the NF-and#954;B signaling cascades. The NF-and#954;B is one of the most important factors involved in the transcription of HIV-1 LTR (Nabel et al., 1987, Asin et al., 2001, Rothwarf et al., 1999). Western blotting and EMSA results indicate that Rv1168c up-regulates p50 and p65 protein expression and its DNA-binding activity. The Rv1168c-mediated increase in HIV-1 LTR activity was found to be predominantly dependent on NF-and#61547;B transcription factor as inhibition of NF-and#61547;B signaling by either treating cells with the specific pharmacological inhibitor, PDTC or by over-expressing phosphorylation defective Iand#61547;Band#945; decrease transcription from the HIV-1 LTR promoter by more than 90% in cells treated with Rv1168c.
Pagination: 247p.
URI: http://hdl.handle.net/10603/5043
Appears in Departments:Centre for DNA Fingerprinting and Diagnostics, Hyderabad

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06_acknowledgement.pdf36.92 kBAdobe PDFView/Open
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09_contents.pdf205.28 kBAdobe PDFView/Open
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11_chapter 1.pdf2.42 MBAdobe PDFView/Open
12_chapter 2.pdf2.01 MBAdobe PDFView/Open
13_chapter 3.pdf2.12 MBAdobe PDFView/Open
14_chapter 4.pdf219.36 kBAdobe PDFView/Open
15_bibliography.pdf319.08 kBAdobe PDFView/Open
16_appendix.pdf205.47 kBAdobe PDFView/Open


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