From viral infection to pulmonary arterial hypertension: a role for viral proteins?
The vascular pathology seen in severe pulmonary arterial hypertension (PAH) is remarkably similar despite the fact that it arises in diverse conditions including idiopathic cases, those associated with collagen vascular diseases, with abnormal blood flow, such as patients with Eisenmenger physiology, and with the use of anorexigen drugs. The pathogenesis of severe PAH is clearly complex, and probably results from the interaction of multiple modulating genes with environmental factors. HIV is evidently a risk factor for the development of PAH, and the increased prevalence of the disease in HIV-infected patients compared with the general population has been noted for several years. The mechanism by which infection leads to full-blown PAH is, however, unknown. Attempts to localize the virus in the vascular lesions or endothelial cells of affected patients have been unsuccessful, suggesting that a direct role of the virus is unlikely, and indicating that the underlying mechanism in pulmonary arterial hypertension associated with HIV (HIV-PAH) is related to the indirect action of infection, possibly through the action of pleiotropic viral proteins. One such candidate HIV protein is one of the first to be detected after invasion of the host cell, Nef. In this article we discuss recent studies on a potential role for Nef in HIV-PAH, with special reference to the knowledge gained from the SIV model of HIV infection.
Victoria Johnson Center for Obstructive Lung Diseases, Virginia Commonwealth University, Richmond, VA, USA. nvoelkel@mcvh-vco.edu
Norbert F
NF
Voelkel
Carlyne D
CD
Cool
Sonia
S
Flores
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004541:Eisenmenger Complex; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000235:genetics; D015497:HIV-1; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D008251:Macaca; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D012307:Risk Factors; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000627:therapeutic use*
D054311:nef Gene Products, Human Immunodeficiency Virus