Human immunodeficiency virus-associated vasculopathy in transgenic mice

Area of Science:

• Vascular Biology
• Infectious Diseases
• Immunology

Background:

• Clinical evidence links human immunodeficiency virus (HIV) infection to vascular disorders, notably vasculitis.
• HIV-associated vasculopathy presents a significant clinical challenge in infected individuals.

Purpose of the Study:

• To investigate the mechanisms underlying HIV-associated vasculopathy using a novel transgenic mouse model.
• To determine the role of specific HIV genes and cell types in vascular pathology.

Main Methods:

• Development of transgenic mice harboring a replication-defective HIV-1 provirus with deletions in gag, pol, and env genes.
• Analysis of vascular changes, including smooth muscle cell migration, proliferation, and inflammatory cell infiltration.
• Assessment of gene expression in vascular tissues and correlation with pathological findings.

Main Results:

• Transgenic mice exhibited extensive vasculopathy, characterized by smooth muscle cell migration and proliferation in blood vessels of all sizes.
• Hypertrophic vessel walls showed infiltration of T cells and plasma cells, predominantly in the adventitia.
• Intimal thickening led to luminal narrowing and tissue ischemia, while the endothelium did not appear to support HIV gene expression.

Conclusions:

• Restricted expression of HIV nonstructural genes in smooth muscle cells is sufficient to induce significant vasculopathy.
• This transgenic model effectively recapitulates key features of HIV-associated vasculopathy, offering a platform for mechanistic studies.
• The findings highlight the critical role of smooth muscle cells and inflammatory responses in the pathogenesis of HIV-related vascular disease.