Occult lymphadenopathic Kaposi's sarcoma associated with severe pulmonary hypertension: A clinical hint about the potential role of HHV-8 in HIV-related pulmonary hypertension?

Gutiérrez, Félix; Masiá, Mar; Padilla, Sergio; Ramos, José Manuel; Bernal, Enrique; Morales, P.; Pozo, Francisco; Andrada, Encarna; Martín-Hidalgo, Alberto

doi:10.1016/j.jcv.2006.05.011

Cited by 12 publications

(4 citation statements)

References 20 publications

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“…Gutierrez and colleagues reported a patient with occult lymphadenopathic Kaposi's sarcoma who developed severe PAH. They speculated on a possible relationship between HHV-8 infection and HIV-associated PAH (38). Finally, Shan and coworkers have recently reported that expression of the HHV-8 gene product viral G protein-coupledreceptor (vGPCR) in human pulmonary artery endothelial cells promoted angiogenesis.…”

Section: Clinical Relevancementioning

confidence: 99%

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Bull¹,

Meadows²,

Coldren³

et al. 2008

Am J Respir Cell Mol Biol

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Human herpesvirus-8 (HHV-8) is the causative agent of Kaposi's sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma and multicentric Castleman's disease. Evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH) has been described. We hypothesize that HHV-8 infection of pulmonary microvascular endothelial cells results in an apoptotic-resistant phenotype characteristic of severe pulmonary arterial hypertension. Our objective was to investigate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells in vitro and characterize the phenotypic effect of this infection. Human pulmonary microvascular endothelial cells were exposed to HHV-8 using two methods (direct virus and co-culture technique). The presence of lytic and latent infection was confirmed. Changes in endothelial cell gene and protein expression and effects on cellular apoptosis were measured. HHV-8 can both lytically and latently infect primary human pulmonary microvascular endothelial cells in vitro. HHV-8 infection results in significant changes in gene expression, including alterations of pathways important to cellular apoptosis. HHV-8 infection also alters expression of genes integral to the bone morphogenic protein pathway, including down-regulation of bone morphogenic protein-4. Other genes previously implicated in the development of PAH are affected by HHV-8 infection, and cells infected with HHV-8 are resistant to apoptosis.

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Section: Clinical Relevancementioning

confidence: 99%

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Bull¹,

Meadows²,

Coldren³

et al. 2008

Am J Respir Cell Mol Biol

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“…Human herpesvirus 8 (HHV-8) is a sexually transmitted pathogen highly prevalent among men who have sex with men [14], although additional transmission routes via saliva, infection during childhood, as well as by blood transfusion, have also been described [15], [16]. HHV-8 is a lymphotropic and vasculotropic herpesvirus linked with Kaposi's sarcoma, and possibly with pulmonary hypertension in HIV-infected patients [17]. Because of the ability of HHV-8-infected vascular endothelial cells to induce the expression of growth factors that cause angiogenesis, endothelial cell proliferation, enhanced vascular permeability, and cytokine production, it had been suggested that HHV-8 could be involved in atherogenesis, but data are very limited [18].…”

Section: Introductionmentioning

confidence: 99%

Coinfection with Human Herpesvirus 8 Is Associated with Persistent Inflammation and Immune Activation in Virologically Suppressed HIV-Infected Patients

et al. 2014

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ObjectivesInfection with co-pathogens is one of the postulated factors contributing to persistent inflammation and non-AIDS events in virologically-suppressed HIV-infected patients. We aimed to investigate the relationship of human herpesvirus-8 (HHV-8), a vasculotropic virus implicated in the pathogenesis of Kaposi's sarcoma, with inflammation and subclinical atherosclerosis in HIV-infected patients.MethodsProspective study including virologically suppressed HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive protein [hsCRP], tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D-dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR), serological tests for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and endothelial function through flow-mediated dilatation of the brachial artery were measured.ResultsA total of 136 patients were included, 34.6% of them infected with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes simplex virus type 2 (HSV-2) (P<0.001), and less frequently with hepatitis C virus (HCV) (P = 0.045), and tended to be older (P = 0.086). HHV-8-infected patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32–7.54] vs 2.08 [0.89–4.11] mg/L, P = 0.009), CD4/CD38/HLA-DR (7.67% [4.10–11.86]% vs 3.86% [2.51–7.42]%, P = 0.035) and CD8/CD38/HLA-DR (8.02% [4.98–14.09]% vs 5.02% [3.66–6.96]%, P = 0.018). After adjustment for the traditional cardiovascular risk factors, HCV and HSV-2 infection, the associations remained significant: adjusted difference between HHV-8 positive and negative patients (95% confidence interval) for hsCRP, 74.19% (16.65–160.13)%; for CD4/CD38/HLA-DR, 89.65% (14.34–214.87)%; and for CD8/CD38/HLA-DR, 58.41% (12.30–123.22)%. Flow-mediated dilatation and total carotid intima-media thickness were not different according to HHV-8 serostatus.ConclusionIn virologically suppressed HIV-infected patients, coinfection with HHV-8 is associated with increased inflammation and immune activation. This might contribute to increase the risk of non-AIDS events, including accelerated atherosclerotic disease.

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“…The HHV-8 antigen was localized in lung tissue of patients with PAH, and interesting case reports have described HIV-PAH in a patient with Castleman disease and Kaposi sarcoma. [63][64][65] In vitro studies have shown that HHV-8 is able to directly infect human microvascular endothelial cells, making them more apoptosis-resistant and disrupting BMPR signaling. 66,67 However, subsequent investigations have not supported an association between HHV-8 and HIV-PAH.…”

Section: Inflammation/immunologic Activationmentioning

confidence: 99%

Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection

George

Singh

Gladwin

2016

Semin Respir Crit Care Med

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The goal of this review is to describe evolving epidemiology of noninfectious, nonneoplastic pulmonary complications of HIV infection, including HIV-associated pulmonary arterial hypertension (HIV-PAH) and interstitial lung disease (ILD). The development of antiretroviral therapy has rendered HIV a chronic illness in treated patients, and the landscape of HIV-associated medical conditions continues to evolve. Although there has been a shift away from AIDS-defining infectious diseases and malignancies, HIV-PAH continues to affect survival adversely when compared with HIV-infected patients without PAH. Studies of pre- and post-highly active antiretroviral therapy (HAART) era show that the prevalence of HIV-PAH remains high and unchanged. The increased prevalence of PAH among HIV-infected individuals has led to several complementary theories about potential mechanisms underlying this disease. Unique mechanisms of HIV-PAH focus on direct effects of viral proteins; alterations in cellular immunologic/inflammatory reactions to the virus; additive effects of cocaine, heroin, and other drugs of abuse; and potentially toxic aspects of antiretroviral and associated therapies. PAH-specific therapy with HAART is likely beneficial in the treatment of HIV-PAH patients. The prevalence of ILD in HIV-infected individuals is also significantly higher than that in the general population. Lymphoid interstitial pneumonitis (LIP) and nonspecific interstitial pneumonia (NSIP) have been reported in both HIV-infected children and adults, and NSIP is more common than LIP in HIV-infected patients. At present, there is no consensus on the pathogenesis of LIP and NSIP in HIV. Finally, we briefly review the literature on venous thromboembolic disease in HIV-infected individuals.

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Occult lymphadenopathic Kaposi's sarcoma associated with severe pulmonary hypertension: A clinical hint about the potential role of HHV-8 in HIV-related pulmonary hypertension?

Cited by 12 publications

References 20 publications

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

Coinfection with Human Herpesvirus 8 Is Associated with Persistent Inflammation and Immune Activation in Virologically Suppressed HIV-Infected Patients

Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection

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