Increased atherosclerosis in HIV-infected humanized mice is caused by a single viral protein, Nef

Authors

• Yongsen Wang, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Beda Brichacek, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Larisa Dubrovsky, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Tatiana Pushkarsky, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Kyle Korolowicz, Departments of Oncology and Radiology, Lombardi Comprehensive Cancer Center and Center for Translational Research, Georgetown University Medical Center, Washington, DC, USA.
• Olga Rodriguez, Departments of Oncology and Radiology, Lombardi Comprehensive Cancer Center and Center for Translational Research, Georgetown University Medical Center, Washington, DC, USA.
• Yichien Lee, Departments of Oncology and Radiology, Lombardi Comprehensive Cancer Center and Center for Translational Research, Georgetown University Medical Center, Washington, DC, USA.
• Marta Catalfamo, Georgetown University Medical Center, Washington DC, USA.
• Chris Albanese, Departments of Oncology and Radiology, Lombardi Comprehensive Cancer Center and Center for Translational Research, Georgetown University Medical Center, Washington, DC, USA.
• Anastas Popratiloff, GW Nanofabrication and Imaging Center, The George Washington University, Washington, DC, USA.
• Dmitri Sviridov, Baker Heart and Diabetes Institute, Melbourne, VIC, 3004, Australia.
• Michael Bukrinsky, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Document Type

Journal Article

Publication Date

4-16-2025

Journal

The Journal of infectious diseases

DOI

10.1093/infdis/jiaf192

Keywords

HIV; Nef; PCSK9; atherosclerosis; humanized mice; inflammation; spectral confocal imaging

Abstract

Antiretroviral therapy (ART) suppresses HIV replication, reverses immunodeficiency, and reduces AIDS-related symptoms, but non-AIDS co-morbidities like cardiovascular diseases remain a major challenge for people living with HIV (PLWH). The pathogenic mechanisms driving these co-morbidities are poorly understood. We previously showed that the HIV protein Nef contributes to chronic inflammation in PLWH. Here, we explored Nef's role in HIV-associated atherosclerosis using a novel model: HIV-infected humanized mice expressing a gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 (PCSK9) and fed a high-fat diet. Comparing atherosclerosis in uninfected mice to those infected with Nef-positive or Nef-deficient HIV-1, we found that Nef exacerbates atherosclerotic changes by increasing inflammation. These results identify Nef as a key driver of HIV-related atherosclerosis and provide a platform for testing therapeutic interventions targeting Nef to mitigate cardiovascular risks in PLWH.

APA Citation

Wang, Yongsen; Brichacek, Beda; Dubrovsky, Larisa; Pushkarsky, Tatiana; Korolowicz, Kyle; Rodriguez, Olga; Lee, Yichien; Catalfamo, Marta; Albanese, Chris; Popratiloff, Anastas; Sviridov, Dmitri; and Bukrinsky, Michael, "Increased atherosclerosis in HIV-infected humanized mice is caused by a single viral protein, Nef" (2025). GW Authored Works. Paper 7042.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7042

Department

Biochemistry and Molecular Medicine