Summary of project PR001492
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001492. The data can be accessed directly via it's Project DOI: 10.21228/M8VX2Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001492 |
| Project DOI: | doi: 10.21228/M8VX2Q |
| Project Title: | Metabolome and transcriptome analysis of oral mucosa of HIV+ patients reveal a role for polyamine metabolic pathway in T cell dysfunction |
| Project Type: | Clinical research |
| Project Summary: | Metabolic changes of immune cells contribute to both physiological and pathophysiological outcomes of immune reactions. How viruses alter the metabolic states of mucosal T cells and the precise mechanisms underlying the persisting immune dysfunction during chronic viral infections are key questions that have not been fully addressed. Here, by comparing transcriptome and salivary metabolome profiles of the uninfected individuals and people living with HIV (PLWH) on treatment, we found a role of polyamine metabolism in immune perturbations of the oral mucosa of HIV+ patients. Flow cytometry analysis confirmed the higher expression of ornithine decarboxylase (ODC-1) and eukaryotic translation initiation factor 5A (EIF5A), the polyamine metabolism intermediates in CD4+ T cells in PLWH. Mechanistic studies using an in vitro human tonsil organoid infection model revealed that HIV infection of activated T cells also resulted in increased polyamine synthesis, which was dependent on the activities of caspase-1, IL-1β, and ODC-1. HIV-1 also led to elevated dysfunctional regulatory T cells (TregDys) /Thelper 17 (Th17) cell ratios as well as heightened expression of ODC-1, EIF5A, and hypusinated EIF5A. Blockade of caspase-1, ODC-1, and EIF5A hypusination and not HIF-1⍺ or NLRP3 reversed the frequency of TregDys showing the direct impact of polyamine pathway in Treg dysfunction during HIV-1 infection. The addition of exogenous polyamines increased TregDys percentages independent of HIV-1 infection in vitro. Finally, oral mucosal TregDys/Th17 ratios and CD4 hyperactivation positively correlated with the increases in salivary putrescine levels, which were found to be elevated in the saliva of PLWH. Thus, by revealing the role of aberrantly increased polyamine synthesis during HIV infection, our study unveils a new mechanism by which chronic viral infections could drive distinct T cell effector programs and Treg dysfunction. |
| Institute: | Case Western Reserve University |
| Department: | Biological Sciences |
| Laboratory: | Pushpa Pandiyan |
| Last Name: | Pandiyan |
| First Name: | Pushpa |
| Address: | Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, 44106 |
| Email: | pxp226@case.edu |
| Phone: | 216-368-2939 |
| Funding Source: | NIH/NIDCR RO1DE026923 |
| Publications: | Under revision |
| Contributors: | Mahalingam SS, Jayaraman S, Bhaskaran N, Schneider E, Faddoul F, Paes da Silva A, Lederman MM, Asaad R, Adkins-Travis K, Shriver LP, and Pandiyan P |
Summary of all studies in project PR001492
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002328 | Metabolome and transcriptome analysis of oral mucosa of HIV+ patients reveal a role for polyamine metabolic pathway in T cell dysfunction | Homo sapiens | Case Western Reserve University | MS | 2022-12-01 | 1 | 66 | Uploaded data (9.7G)* |
