Pathogenesis of HIV-associated pulmonary hypertension: potential role of HIV-1 Nef.
Enviado por Sharilyn Almodovar el
Título | Pathogenesis of HIV-associated pulmonary hypertension: potential role of HIV-1 Nef. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Autores | Almodóvar, S, Hsue, PY, Morelli, J, Huang, L, Flores, SC |
Corporate Authors | Lung HIV Study |
Journal | Proc Am Thorac Soc |
Volume | 8 |
Issue | 3 |
Pagination | 308-12 |
Date Published | 2011 Jun |
ISSN | 1943-5665 |
Palabras clave | Down-Regulation, Echocardiography, Electrocardiography, Endothelium, Female, Genetic Markers, Heart Catheterization, HIV Infections, Humans, Hypertension, Pulmonary, Lung, Male, Middle Aged, Mutation, nef Gene Products, Human Immunodeficiency Virus, Protein Multimerization, Protein Transport, Sequence Analysis, Protein, tat Gene Products, Human Immunodeficiency Virus |
Abstract | Infection with HIV increases the risk for lung diseases, including noninfectious pulmonary hypertension (PH). HIV-associated PH (HIV-PH) is an important lung disease in HIV-infected persons who live longer with antiretrovirals. The early stages of HIV-PH may be overlooked by healthcare providers due to nonspecific symptoms, including progressive dyspnea and nonproductive cough. HIV-PH may be detected via chest radiographs, CT scans, or electrocardiograms, but Doppler echocardiography is the most useful screening test to identify candidates for right heart catheterization. HIV-PH has a poor prognosis with high mortality; improved biomarkers to identify earlier stages of PH would benefit clinical care. The HIV-PH mechanism remains unknown, but HIV proteins such as Tat and Nef may play a role. HIV-1 Nef is a broad-spectrum adaptor protein that may affect HIV-infected and uninfected pulmonary vascular cells. Studies in macaques suggest that Nef is important in HIV-PH pathogenesis because monkeys infected with a chimeric simian immunodeficiency virus (SIV) expressing HIV-nef (SHIVnef) alleles, but not monkeys infected with the native SIV, develop pulmonary vascular remodeling. Four consistent amino acid mutations arose spontaneously in Nef passaged in the monkeys. To translate these findings to humans, one research endeavor of the Lung HIV Study focuses on the identification of HIV nef mutations in HIV-infected individuals with PH compared with HIV-infected normotensive patients. We present some of the preliminary evidence. Ongoing longitudinal studies will establish the connection between Nef mutations and the propensity for HIV-PH. |
DOI | 10.1513/pats.201006-046WR |
Alternate Journal | Proc Am Thorac Soc |
PubMed ID | 21653533 |