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Association of cell free mitochondrial DNA and caspase-1 expression with disease severity and ARTs efficacy in HIV infection

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Abstract

HIV infection is a global health concern. Current HIV-diagnostics provide information about the disease progression and efficacy of anti-retroviral therapies (ARVs), but this information is very limited and sometimes imprecise. Present study assessed the potential role of mononuclear cell (MNC) death, expression of caspases (1&3) and cell free mitochondrial DNA (CF mt-DNA) in HIV infected individuals. Apoptosis, cell-count, expression of caspases and CF mt-DNA were measured through flow cytometry and qPCR, respectively, in HIV infected individuals (n = 120) divided in two groups i.e. ARVs-receiving (treated, n = 87), ART-naïve (untreated, n = 37) and healthy individuals (n = 47). Data showed significant (p < 0.0001) cell death in untreated individuals than treated and healthy individuals. CD4-positive T-cell percentage declined (p < 0.0001) in untreated as compared to treated individuals. Caspase-1, an indicator of pyroptosis, and CF mt-DNA were also elevated in untreated HIV infected individuals. Untreated individuals when administered with ARVs showed improved CD4-positive T-cell percentage, lower caspase-1, CF mt-DNA and cell death. Data elucidated positive co-relation between cell death and CF mt-DNA in treated and untreated HIV infected individuals. While CD4-positive T-cell percentage was negatively correlated with caspase-1 expression and CF mt-DNA. Elevated levels of CF mt-DNA and caspase-1 in HIV infected individuals, positive correlation between cell death and CF mt-DNA, negative correlation of CD4-positive T-cell percentage with CF mt-DNA and caspase-1 expression clearly indicated the potential of CF mt-DNA and caspase-1 as a novel disease progression and ARTs effectiveness biomarkers in HIV.

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Data availability

All the relevant data points are included in the manuscript. For acquisition of raw data, please contact Mariam Anees (mariam@qau.edu.pk).

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Acknowledgements

We are thankful to Mr. Asghar Satti, Mr. Uzair Tariq, Miss Kalsoom Zahra and Mr. Ramzan from Association of People Living with HIV (APLHIV) Pakistan for their kind help in sampling and provision of necessary data.

Funding

The project has been supported financially by Higher Education Commission Grant No. NRPU 4481 to M. A. Research associate funding was provided to ZA in the same project.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, University Road, Islamabad, 45320, Pakistan

    Zain Ali, Iram Shahzadi, Sidra Bukhari & Mariam Anees

  2. Alpha Genomics (Pvt) Ltd., Islamabad, Pakistan

    Shahid Waseem & Ibrar Ahmed

  3. Institute of Diet and Nutritional Sciences, University of Lahore, Islamabad Campus, Islamabad, Pakistan

    Riffat Aysha Anis

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  1. Zain Ali
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Ali, Z., Waseem, S., Shahzadi, I. et al. Association of cell free mitochondrial DNA and caspase-1 expression with disease severity and ARTs efficacy in HIV infection. Mol Biol Rep 48, 3327–3336 (2021). https://doi.org/10.1007/s11033-021-06313-0

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