Expression of human herpesvirus 8 in primary pulmonary hypertension.
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.
D052006:Bone Morphogenetic Protein Receptors, Type II; D016213:Cyclins / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000150:complications* / Q000175:diagnosis; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000821:virology*; D008168:Lung / Q000821:virology*; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017422:Sequence Analysis, DNA; D014764:Viral Proteins
D016213:Cyclins; D004279:DNA, Viral; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II