ArticleAIDS research and human retroviruses2012
Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension.
Article in AIDS research and human retroviruses, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- NF-κB-dependent and independent inflammatory responses during acute HIV-1 infection in a model of human microglia.Frontiers in immunology · 2026Article
- 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
- The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2025Review
- The Intersection of HIV and Pulmonary Vascular Health: From HIV Evolution to Vascular Cell Types to Disease Mechanisms.Journal of vascular diseases · 2024Article
- HIV-Associated Hypertension: Risks, Mechanisms, and Knowledge Gaps.Circulation research · 2024Review
- Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension.Frontiers in immunology · 2022Article
- Impact of human immunodeficiency virus on pulmonary vascular disease.Global cardiology science & practice · 2021Review
- 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
- The DNA Damage Response and HIV-Associated Pulmonary Arterial Hypertension.International journal of molecular sciences · 2020Review
- HIV-1 Nef promotes cell proliferation and microRNA dysregulation in lung cells.Cell cycle (Georgetown, Tex.) · 2019Article
- Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques.Viral immunology · 2018Article
- Pulmonary disease in HIV-infected adults in the era of antiretroviral therapy.AIDS (London, England) · 2018Review
- HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease.Frontiers in cardiovascular medicine · 2018Review
- Cardiovascular Complications of HIV in Endemic Countries.Current cardiology reports · 2016Review
- Maintaining lung health with longstanding HIV.Current opinion in infectious diseases · 2016Review
- Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.PloS one · 2016Article
- Pulmonary Arterial Hypertension among HIV-Infected Children: Results of a National Survey and Review of the Literature.Frontiers in pediatrics · 2015Review
- Risk of echocardiographic pulmonary hypertension in individuals with human immunodeficiency virus-hepatitis C virus coinfection.Annals of the American Thoracic Society · 2014Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Severe pulmonary hypertension (PH) associated with vascular remodeling is a long-term complication of HIV infection (HIV-PH) affecting 1/200 infected individuals vs. 1/200,000 frequency in the uninfected population. Factors accounting for increased PH susceptibility in HIV-infected individuals are unknown. Rhesus macaques infected with chimeric SHIVnef virions but not with SIV display PH-like pulmonary vascular remodeling suggesting that HIV-Nef is associated with PH; these monkeys showed changes in nef sequences that correlated with pathogenesis after passage in vivo. We further examined whether HIV-nef alleles in HIV-PH subjects have signature sequences associated with the disease phenotype. We evaluated specimens from participants with and without HIV-PH from European Registries and validated results with samples collected as part of the Lung-HIV Studies in San Francisco. We found that 10 polymorphisms in nef were overrepresented in blood cells or lung tissue specimens from European HIV-PH individuals but significantly less frequent in HIV-infected individuals without PH. These polymorphisms mapped to known functional domains in Nef. In the validation cohort, 7/10 polymorphisms in the HIV-nef gene were confirmed; these polymorphisms arose independently from viral load, CD4(+) T cell counts, length of infection, and antiretroviral therapy status. Two out of 10 polymorphisms were previously reported in macaques with PH-like pulmonary vascular remodeling. Cloned recombinant Nef proteins from clinical samples down-regulated CD4, suggesting that these primary isolates are functional. This study offers new insights into the association between Nef polymorphisms in functional domains and the HIV-PH phenotype. The utility of these polymorphisms as predictors of PH should be examined in a larger population.
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