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The role and impact of Nef and Nef inhibitor in HIV-induced impairment of CD4 T-cells

Mahesh, Deepika (2024) The role and impact of Nef and Nef inhibitor in HIV-induced impairment of CD4 T-cells. Master's Thesis, University of Pittsburgh. (Unpublished)

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This study, utilizing in vitro models, aims to examine the effects of Nef and its inhibitors on the impairment of CD4 T cells induced by HIV. The primary objectives are to uncover the mechanism by which Nef impacts CD4 T cells and to assess the therapeutic viability of Nef inhibitors. Using the CEM-T4 cell line, we investigated the impact of Nef on CD4 expressions. Our findings demonstrate that Nef causes a decrease in CD4 expression. However, using the Nef inhibitor B9 at different concentrations, we observed an improvement in CD4 expression. These results suggest that Nef inhibitors can potentially mitigate the harmful effects of Nef on CD4 T cells. Our study delved into the effects of Nef on HIV-infected human primary CD4 T cells isolated from peripheral blood mononuclear cells (PBMCs), exploring various strains of HIV and administering the Nef inhibitor B9. Our findings highlight the promising potential of Nef inhibitors as a therapeutic intervention. Treatment with the Nef inhibitor effectively reduced viral replication and Nef protein expression levels. Additionally, we assessed the cytokine responses induced by HIV infection and its modulation by Nef inhibitors. Treatment with the Nef inhibitor resulted in a cytokine response similar to that of uninfected cells, indicating its ability to mitigate the immune response triggered by HIV infection. This underscores the need for further investigation into the mechanisms underlying HIV-induced immune dysregulation. This research provides insights into the potential use of Nef inhibitors as therapeutic interventions, particularly in modulating immune responses within PBMCs. The knowledge gained from this may contribute to a deeper understanding of HIV pathogenesis and develop novel strategies for combating this global health challenge.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Mahesh, Deepikadem215@pitt.edudem215
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMailliard, Robbie Brbm19@pitt.edurbm19
Committee MemberDa Silva Castanha, Priscila Mayrellepmd35@pitt.edupmd35
Committee MemberMcMillen, Cynthia Mcmm287@pitt.educmm287
Date: 16 May 2024
Date Type: Publication
Defense Date: 19 April 2024
Approval Date: 16 May 2024
Submission Date: 25 April 2024
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 77
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: 1. HIV 2. Nef 3. CD4 T cells 4. In vitro models 5. Nef inhibitors 6. CEM-T4 cell line 7. CD4 expression 8. B9 inhibitor 9. Viral replication 10. Immune response 11. Peripheral blood mononuclear cells (PBMCs) 12. HIV pathogenesis 13. Immune dysregulation 14. Therapeutic intervention 15. Cytokine responses 16. Immune modulation 17. HIV strains 18. Nef protein expression 19. Immune system 20. HIV therapy
Date Deposited: 16 May 2024 19:45
Last Modified: 16 May 2024 19:45


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