ArticleAmerican journal of respiratory and critical care medicine2006
HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques.
Article in American journal of respiratory and critical care medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 182 citations in OpenAlex.
- HIV-Associated Pulmonary Arterial Hypertension in Resource-Limited Settings: A "Forgotten" Diagnosis, a Great Imitator, and a Multi-Hit Pulmonary Vasculopathy.Pulmonary circulation · 2026Review
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- Evaluation of Cardiac Findings in People With Human Immunodeficiency Virus.Anatolian journal of cardiology · 2025Article
- Role of HIV-encoded proteins in cardiovascular disease.American journal of physiology. Cell physiology · 2025Review
- Differential Effects of Human Immunodeficiency Virus Nef Variants on Pulmonary Vascular Endothelial Cell Dysfunction.Infectious disease reports · 2025Article
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- HIV Protein Nef Induces Cardiomyopathy Through Induction of Bcl2 and p21.International journal of molecular sciences · 2024Article
- The Intersection of HIV and Pulmonary Vascular Health: From HIV Evolution to Vascular Cell Types to Disease Mechanisms.Journal of vascular diseases · 2024Article
- Review
- HIV and Drug Use: A Tale of Synergy in Pulmonary Vascular Disease Development.Comprehensive Physiology · 2023Article
- Novel role of HIV-1 Nef in regulating the ubiquitination of cellular proteins.Frontiers in cellular and infection microbiology · 2023Article
- Article
- Review
- The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure.Circulation research · 2022Review
- Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension.Frontiers in immunology · 2022Article
- Association between HIV and incident pulmonary hypertension in US Veterans: a retrospective cohort study.The lancet. Healthy longevity · 2021Article
- Impact of human immunodeficiency virus on pulmonary vascular disease.Global cardiology science & practice · 2021Review
- Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension.Advances in experimental medicine and biology · 2021Article
- Dysregulation of the Immune Environment in the Airways During HIV Infection.Frontiers in immunology · 2021Article
- HIV X4 Variants Increase Arachidonate 5-Lipoxygenase in the Pulmonary Microenvironment and are associated with Pulmonary Arterial Hypertension.Scientific reports · 2020Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
rationaleHIV-infected patients with pulmonary arterial hypertension have histologic manifestations that are indistinguishable from those found in patients with idiopathic pulmonary arterial hypertension. In addition, the role of pleiotropic viral proteins in the development of plexiform lesions in HIV-related pulmonary hypertension (HRPH) has not been explored. Simian immunodeficiency virus (SIV) infection of macaques has been found to closely recapitulate many of the characteristic features of HIV infection, and thus hallmarks of pulmonary arterial hypertension should also be found in this nonhuman primate model of HIV.
objectivesTo determine whether pulmonary arterial lesions were present in archived SIV-infected macaque lung tissues from Johns Hopkins University and two National Primate Research Centers.
methodsArchived macaque and human lung sections were examined via immunohistochemistry for evidence of complex vascular lesions.
resultsComplex plexiform-like lesions characterized by lumenal obliteration, intimal disruption, medial hypertrophy, thrombosis, and recanalized lumena were found exclusively in animals infected with SHIV-nef (a chimeric viral construct containing the HIV nef gene in an SIV backbone), but not in animals infected with SIV. The mass of cells in the lesions were factor VIII positive, and contained cells positive for muscle-specific and smooth muscle actins. Lung mononuclear cells were positive for HIV Nef, suggesting viral replication. Endothelial cells in both the SHIV-nef macaques and patients with HRPH, but not in patients with idiopathic pulmonary arterial hypertension, were also Nef positive.
conclusionsThe discovery of complex vascular lesions in SHIV-nef- but not SIV-infected animals, and the presence of Nef in the vascular cells of patients with HRPH, suggest that Nef plays a key role in the development of severe pulmonary arterial disease.
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