Year: 2017
Type: editorial
Abstract: ulmonary arterial hypertension (PAH) is a deleterious disease of the lung vasculature characterized by endothelial dysfunction, medial hypertrophy and proliferation, and eventual occlusion of the pulmonary arterioles.Although a number of genetic and environmental triggers have been described as causative, the specific molecular origins of this vascular disease are still unknown.Multiple lines of evidence now converge to connect immune dysregulation to PAH in humans and animal models.Previous reports suggest that altered inflammatory dynamics, such as hematopoietic and myeloid expansion, B-and T-cell dysfunction, increased cytokine production, circulating autoantibodies, and tertiary lymphoid tissue neogenesis, may initiate or drive PAH. 1 Clinically, a well-established causative link exists between autoimmune connective tissue disorders and PAH.Furthermore, infectious agents, such as Schistosoma mansoni and human immunodeficiency virus (HIV), are known to alter the immune cell repertoire and predispose to the development of PAH.However, a mechanistic understanding of the exogenous or endogenous factors that drive immune dysfunction remains largely undefined.Prior studies have aimed to characterize the role of exogenous viruses in PAH.For example, HIV-associated PAH has been attributed to decreased CD4+ T-cell function, indicating a role for T-cell-mediated immune dysregulation. 2 Separately, HIV-encoded proteins such as Nef have been reported to be pleiotropic meditators promoting inflammation and endothelial dysfunction in PAH, independent of vascular infection.Human herpesvirus 8 infection, often observed coincident with HIV, is the causative agent for Kaposi sarcoma-tumors characterized by endothelial hyperproliferation with histology similar to that observed in plexiform lesions of end-stage PAH.A role for humanherpes virus 8 in PAH was proposed by demonstrating upregulation of human herpes virus 8 viral protein and genomic expression in PAH lung tissue.3 However, these results have not been observed in separate, larger patient cohorts.4 Additionally, connections have been proposed between PAH and chronic infection of Epstein-Barr virus and hepatitis C virus.In this issue of Circulation, Saito et al 5 present evidence supporting a novel model of pathogenesis, implicating an endogenous, rather than an exogenous, retrovirus in the inflammatory processes of PAH.Human endogenous retroviruses (HERVs) are ancestral proviruses classified as mobile genetic elements.Although these viruses no longer replicate, they can be transmitted vertically and are activated by infection or other stressors.Activation may lead to transcription or mobilization of HERV genes, resulting in functional abnormalities and chromosomal instability.6 HERV-K sequences are transcriptionally active and have been associated with chronic inflammatory conditions such as cancer, 6 neurological disorders, and other autoimmune diseases. Human Endogenous Retrovirus K and Pulmonary Arterial HypertensionA New Take on a Retro Idea
Source: Circulation
Authors: Miranda K. Culley, Stephen Y. Chan
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2769926510