ORCID

0009-0006-3616-3778

Keywords

oxidative stress, HIV latency, iron accumulation, lipid metabolism, antioxidant enzymes, apigenin

Abstract

Human immunodeficiency virus (HIV) impacts over 39 million people worldwide. Advanced antiretroviral therapy suppresses viral replication but fails to eliminate the virus from the host. People living with HIV (PLWH) experience various HIV-related comorbidities, including cardiovascular disease, inflammatory disorders, and neurodegeneration. The mechanisms through which viral proteins influence cellular dysfunction are still under investigation. Current in vitro HIV models use immune-derived cell lines that do not fully represent the effects of latent HIV on other tissues. To address this gap, we created a novel mouse embryonic fibroblast (MEF) stable cell line using HIV transgenic mice (Tg26). The Tg26 MEF cell line expresses HIV genes without generating an infectious virus, making it an ideal model to study the impact of HIV on cells during latency. In our study, we found that Tg26 MEF cells show increased accumulation of iron and lipid species, as well as higher expression of proteins involved in iron and lipid accumulation compared to wild-type (WT) MEF cells. Further analysis of oxidative stress markers in Tg26 MEF cells shows elevated reactive oxygen species (ROS) formation and downregulation of key antioxidant enzymes. Moreover, our study found that treatment with antioxidant compound apigenin diminishes iron accumulation and restores expression of antioxidant enzymes, indicating a protective effect against oxidative stress in Tg26 MEF cells. Collectively, these findings illustrate that the expression of HIV genes in MEF cells induces oxidative stress, disrupts redox balance, induces lipid stress, and disturbs iron homeostasis. Ultimately, this primes the cells for a unique metabolic stage that may enable HIV to persist longer in its latent form in these cells. The Tg26 MEF cell line provides a novel and valuable in vitro model to investigate the molecular basis of HIV latency at the cellular level and the development of new therapies to reduce HIV-induced comorbidities in PLWH.

Completion Date

2025

Semester

Summer

Committee Chair

Gupta, Manish

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Release Date

8-15-2027

Document Type

Thesis

Campus Location

College of Medicine

Subjects

HIV infections--Animal models; HIV (Viruses)--Research; HIV infections--Research; Retrovirus infections--Animal models; HIV infections--Pathogenesis

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