Human Immunodeficiency Virus<i>nef</i>Signature Sequences Are Associated with Pulmonary Hypertension

Almodóvar, Sharilyn; Knight, Rob; Allshouse, Amanda A.; Roemer, Sarah C.; Lozupone, Catherine; McDonald, Daniel; Widmann, Jeremy; Voelkel, Norbert F.; Shelton, Robert J.; Suarez, Edu; Hammer, Kenneth W.; Goujard, Cécile; Petrosillo, Nicola; Simonneau, Gérald; Hsue, Priscilla Y.; Humbert, Marc; Flores, Sonia C.

doi:10.1089/aid.2011.0021

Cited by 55 publications

(48 citation statements)

References 41 publications

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“…Nef is also responsible for T cell activation in infected cells [61, 62] and enhances virus production in vivo [63]. In fact, transgenic mice expressing CD4-promoter-driven Nef develop a spectrum of pathologies including AIDS-like disease [64] and vasospasm in the heart [65], and certain Nef gene variants were linked to pulmonary hypertension [66, 67]. We have recently reported that HIV-infected T cells are more potent than free virus in activating coronary arterial endothelial cells [68].…”

Section: Endothelial Dysfunction In Hiv Patientsmentioning

confidence: 99%

Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat

Wang¹,

Yi²,

Green³

et al. 2015

Cardiovascular Pathology

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With effective antiretroviral therapy (ART), many HIV-infected people die of diseases other than acquired immune deficiency syndrome (AIDS). In particular, coronary artery disease has emerged as one of most critical complications of HIV infection and a major cause of morbidity and mortality. Although reportedly antiretroviral combination therapy itself may accelerate atherosclerosis by enhancing dyslipidemia, most recent epidemiological studies support the notion that HIV infection itself contributes to cardiovascular disease. However, it is still a mystery how the virus can contribute to cardiovascular disease development even while suppressed by ARTs. This review discusses the current understanding of interactions between HIV infection and cardiovascular diseases in both clinical and experimental studies with special focus on those viral proteins which are still produced by HIV. This will help infectious disease/vascular biology experts to gain insights into the pathophysiological mechanisms of HIV associated cardiovascular disease and new trends to treat and prevent cardiovascular disease in the HIV infected population.

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Section: Endothelial Dysfunction In Hiv Patientsmentioning

confidence: 99%

Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat

Wang¹,

Yi²,

Green³

et al. 2015

Cardiovascular Pathology

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“…20,21 Specific nef signature sequences have been associated with PAH in 2 different HIV cohorts. 22 Bone morphogenic protein receptor 2 (BMPR-2) mutations are associated with familial PAH and result in decreased signaling through BMPR-2. 23 The HIV-1 tat (transcriptional transactivator) protein represses BMPR-2 gene expression in human macrophages in vitro, interfering with BMP–BMPR-2 transcriptional regulation.…”

Section: Pathogenesismentioning

confidence: 99%

Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension

Barnett

Hsue

2013

Clinics in Chest Medicine

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“…Although rare, PH complicating HIV infection has not decreased appreciably with available antiretroviral therapy (ART), and the mechanistic link between PH and HIV has not been clearly established (4). Although HIV ribonucleic acid (RNA) has not been isolated in the pulmonary vasculature, HIV proteins such as Tat and Nef cause endothelial dysfunction (6)(7)(8)(9)(10)(11)(12). It stands to reason that other viral infections may cause downstream fibroproliferation and remodeling in the pulmonary circulation.…”

mentioning

confidence: 99%

Risk of Echocardiographic Pulmonary Hypertension in Individuals with Human Immunodeficiency Virus–Hepatitis C Virus Coinfection

et al. 2014

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Rationale: Human immunodeficiency virus (HIV) infection is a risk factor for pulmonary hypertension (PH). Chronic hepatitis C virus (HCV) infection may have unique or synergistic effects on the pulmonary vasculature, but the prevalence and risk factors for PH in HIV-HCV coinfected persons are not known.Objectives: To define the prevalence of echocardiographic PH in a cohort of patients with HIV-HCV coinfection, to compare this estimate with the reported prevalence of PH among those with HIV infection alone, and to identify potential risk factors for PH in coinfected individuals.Methods: We performed a retrospective study of HIV-HCV coinfected patients followed at our institution from 2003 to 2012 with evidence of HCV infection (positive HCV antibody, measurable HCV ribonucleic acid viral load, and/or genotype) within 6 months of transthoracic echocardiogram. PH was defined by an estimated pulmonary artery systolic pressure (PASP) of greater than or equal to 40 mm Hg or more than moderate right ventricular dysfunction. We excluded those diagnosed with cirrhosis, left ventricular ejection fraction less than 50%, or more than moderate aortic or mitral valve disease. Measurements and Main Results:Sixty-eight patients were included, and 43 had adequate estimates of PASP. The median (interquartile range) age was 52 (48-57) years, and 45 (67%) were men. Eight (19%) had PH, and three (7%) had more than moderate right ventricular dysfunction. After age and sex adjustment, interferon (IFN)-based HCV treatment was associated with higher PASP (b, 6.00 mm Hg; 95% confidence interval, 0.09-11.90; P = 0.047) and with the risk of PH (odds ratio, 5.65; 95% confidence interval, 1.07-29.93; P = 0.042). These associations persisted after adjustment for comorbidities but were attenuated by adjustment for duration of HCV diagnosis. Conclusions:The prevalence of echocardiographic PH may be higher in HIV-HCV coinfected individuals than in those with HIV monoinfection. IFN-based HCV treatment and time since HCV diagnosis were associated with the development of PH as assessed by echocardiography. Further studies are needed to examine HIV-HCV coinfection, HCV treatment, and duration of infection as possible causes of pulmonary vascular disease.

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Human Immunodeficiency VirusnefSignature Sequences Are Associated with Pulmonary Hypertension

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.

Cited by 55 publications

References 41 publications

Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat

Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat

Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension

Risk of Echocardiographic Pulmonary Hypertension in Individuals with Human Immunodeficiency Virus–Hepatitis C Virus Coinfection

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