# Primary role of Golgi stress in anti-HIV drug and alcohol abuse-induced hepatotoxicity

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $412,500

## Abstract

Anti-HIV or HIV-HCV/HBV co-infection drugs help people with HIV/AIDS live longer and healthier
lives. However, the HIV medicines often cause side effects. Although most side effects from the HIV
medicines are manageable, a few such as damages to the liver can be very serious and life
threatening. To be worse, nearly half of the HIV infected patients abuse/consume alcohol or having a
multiple drug-abuse problem, which not only impairs patients’ adherence to the anti-HIV therapy but
also deteriorates antiviral-induced hepatotoxicity leading to greater morbidity and mortality. Hence
molecular mechanisms and potential therapeutic targets underlying the hepatotoxicity are under
intense investigations. Previous studies by us and others suggest that endoplasmic reticulum (ER)
stress contributes to HIV protease inhibitors and/or alcohol abuse-induced hepatic cell death,
steatohepatitis and cirrhosis in animal models and patients. However, therapies to ensure proper ER
homeostasis such as applications of chemical chaperones, antioxidants, autophagy inducers, or
selective enhancement of protective ER signaling pathways only yield partial effects in a variety of in
vitro and in vivo model systems, which suggest that other more precise cellular targets are involved in
the anti-HIV drugs and/or alcohol-induced hepatotoxicity. Our most recent studies reveal a strong
effect of certain HIV protease inhibitors on the ER-Golgi trafficking and integrity of the Golgi
apparatus, which occurs earlier than the ER stress response and results in increased cell death
compared to the cell death induced by pharmaceutical ER stress inducing agents. Herein we
hypothesize that the anti-HIV drugs target primarily at the Golgi apparatus and dysfunction of Golgi
triggers other organelle stress response leading to liver disease development, which is deteriorated
by alcohol-induced ER stress response. We propose to: (1) identify specific molecular components of
the ER-Golgi traffic machineries that are affected by the anti-HIV drugs and/or alcohol; (2) investigate
mechanisms that regulate the drug-induced Golgi stress response; (3) study how the Golgi stress
mediates downstream hepatic injury; (4) evaluate cytoprotective effects of therapies targeting the
Golgi stress. This project will provide a scientific basis for a better care for HIV/AIDS patients
suffering from liver damages resulted from anti-HIV drugs and alcohol abuse.

## Key facts

- **NIH application ID:** 10160856
- **Project number:** 5R01DA042632-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** CHENG JI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160856

## Citation

> US National Institutes of Health, RePORTER application 10160856, Primary role of Golgi stress in anti-HIV drug and alcohol abuse-induced hepatotoxicity (5R01DA042632-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10160856. Licensed CC0.

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