Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 2003 Sep 18;349(12):1113-22
Date
09/19/2003Pubmed ID
13679525DOI
10.1056/NEJMoa035115Scopus ID
2-s2.0-0141679188 (requires institutional sign-in at Scopus site) 260 CitationsAbstract
BACKGROUND: Severe pulmonary hypertension constitutes a group of diseases characterized by complex, lumen-occluding vascular lesions that develop in genetically susceptible persons. The only viral infection associated with severe pulmonary hypertension has been that due to human immunodeficiency virus type 1, but neither the viral genome nor viral antigens have been demonstrated in pathologic lesions.
METHODS: We examined lung-tissue samples from 16 patients with sporadic primary pulmonary hypertension and 14 patients with secondary pulmonary hypertension for evidence of infection with human herpesvirus 8 (HHV-8). HHV-8 infection was ascertained immunohistochemically with use of an antibody directed against latency-associated nuclear antigen 1 (LANA-1), and a polymerase-chain-reaction (PCR) assay was performed on lung DNA to detect the viral cyclin gene of HHV-8. Sequence analysis was also performed.
RESULTS: In lung tissue from 10 of 16 patients with primary pulmonary hypertension (62 percent), cells within the plexiform lesions as well as cells outside the lesions were positive for LANA-1 on immunohistochemical analysis. Tissue from the same 10 patients contained viral cyclin on PCR analysis. No LANA-1 was detected in lung tissue from patients with secondary pulmonary hypertension, although one such patient had PCR evidence of viral cyclin. Plexiform lesions from patients with primary pulmonary hypertension had a histologic and immunohistochemical resemblance to cutaneous Kaposi's sarcoma lesions.
CONCLUSIONS: The spectrum of trigger factors and molecular mechanisms leading to severe pulmonary hypertension and the formation of plexiform lesions is apparently wide, including both genetic and epigenetic factors. Our data suggest that infection with the vasculotropic virus HHV-8 may have a pathogenetic role in primary pulmonary hypertension.
Author List
Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, Geraci MW, Brown KK, Routes JM, Tuder RM, Voelkel NFAuthor
John M. Routes MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Bone Morphogenetic Protein Receptors, Type IICyclins
DNA, Viral
Female
Genes, Viral
Herpesviridae Infections
Herpesvirus 8, Human
Humans
Hypertension, Pulmonary
Lung
Male
Mutation
Sequence Analysis, DNA
Viral Proteins
