Human γ-Herpesviruses Epstein-Barr Virus and Human Herpesvirus-8 Are Not Detected in the Lungs of Patients With Severe Pulmonary Arterial Hypertension

Abstract

In susceptible individuals, multiple events may trigger pulmonary vascular remodeling and pulmonary arterial hypertension (PAH). Human herpesvirus-8 (HHV-8), a γ-herpesvirus homologous with Epstein-Barr virus (EBV), was suggested to act as a "second hit" in the development of PAH in susceptible patients. Although there is indirect evidence from in vitro and animal studies in favor of a link between γ-herpesviruses and the pathophysiology of PAH, results remain controversial. Therefore, we investigated the presence of EBV and HHV-8 in the lungs of patients with PAH. Thirty-four lungs explanted from French patients with end-stage PAH (mean age, 38 ± 14 years; 19 women) were studied. Tissue samples were incorporated into tissue microarrays. Normal lung tissues served as negative controls. Kaposi sarcoma tissue served as a positive control for HHV-8, and EBV-associated lymphoma served as a positive control for EBV. The presence of HHV-8 was investigated with immunohistochemistry and polymerase chain reaction. The presence of EBV was investigated with immunohistochemistry and in situ hybridization. For HHV-8, none of PAH lung samples showed a "stippling" nuclear pattern classically observed in HHV-8-positive Kaposi sarcoma lesions. When studied by polymerase chain reaction, all cases remained negative. For EBV, none of the PAH lung samples showed positive staining, whatever the technique applied. HHV-8 and EBV cannot be detected in the lungs of patients with end-stage PAH. The role of these γ-herpesviruses in the pathophysiology of PAH is, therefore, unlikely.