Increased Atherosclerosis in HIV-Infected Humanized Mice Is Caused by a Single Viral Protein, Nef
Year: 2025
Type: article
Abstract: Antiretroviral therapy suppresses human immunodeficiency virus (HIV) replication, reverses immunodeficiency, and reduces AIDS-related symptoms, but non-AIDS comorbidities like cardiovascular diseases remain a major challenge for people with HIV (PWH). The pathogenic mechanisms driving these comorbidities are poorly understood. We previously showed that the HIV protein Nef contributes to chronic inflammation in PWH. 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 PWH.
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Awards: G145812530, G203415456, Acquisition of Zeiss Cell Observer Spinning Disk Confocal System, Acquisition of Zeiss 710 Confocal Laser Scanning Microscope, Preclinical Imaging - Bruker 70/30USR BioSpec Magnet, G9000129367, G9000226715, G9000273067, District of Columbia Center for AIDS Research, Georgetown University Lombardi Comprehensive Cancer Center Support Grant
OpenAlex ID: W4409484628