Iyer, K and Mitra, A and Mitra, D (2023) Identification of 5' upstream sequence involved in HSPBP1 gene transcription and its downregulation during HIV-1 infection. Virus Research, 324. p. 199034.

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Abstract

The Human Immunodeficiency Virus-1 (HIV-1) is known to modulate the host environment for successful replication and propagation like other viruses. The virus utilises its proteins to interact with or modulate host factors and host signalling pathways that may otherwise restrict the virus. A previous study from our lab has shown that the host heat shock protein 70 (HSP70) binding protein (HSPBP1) is a co-chaperone that inhibits viral replication. We have also shown that the virus downregulates HSPBP1 during infection. However, the mechanism of downregulation remains to be elucidated. In the present study, we hypothesized that the HSPBP1 promoter may be repressed during infection leading to its downmodulation at the RNA and protein levels. The 5’ upstream region of the HSPBP1 gene was first mapped and it was identified that a fragment comprising of a ∼600 bp upstream region of the transcription start site show the highest promoter-like activity. Further, the Sp1 transcription factor was shown to be essential for normal promoter activation. Our results further demonstrate that HIV-1 downregulates the activity of the identified promoter. It was seen that the viral transactivator protein, Tat, was responsible for the downmodulation of the HSPBP1 promoter. HIV-1 Tat is known to bind and regulate several cellular promoters during infection, thereby making the environment conducive for establishment of the virus. Our results further show that Tat is recruited to the HSPBP1 promoter and in the presence of Tat, recruitment of Sp1 on HSPBP1 promoter was decreased, which explains the suppression of HSPBP1 during HIV-1 infection. Therefore, this study further adds to the list of cellular promoters that are modulated by Tat during HIV-1 infection either directly or indirectly.

Item Type:	Article
Additional Information:	National Centre for Cell Science, NCCS Complex, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, Maharashtra 411007, India
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	06 Feb 2023 12:09
Last Modified:	08 Feb 2023 10:50
URI:	http://nccs.sciencecentral.in/id/eprint/1241

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