Human γ-herpesviruses Epstein-Barr virus and human herpesvirus-8 are not detected in the lungs of patients with severe pulmonary arterial hypertension.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Service d'Anatomie Pathologique and INSERM U563, Centre Hospitalier Universitaire Purpan, Toulouse; Service d'Anatomie Pathologique, Centre Hospitalier Universitaire Jean Minjoz, Besançon.
Séverine
S
Valmary
INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson; AP-HP, Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Antoine Béclère, Clamart; Université Paris-Sud, Faculté de médecine, Kremlin Bicêtre, France.
Peter
P
Dorfmüller
INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson; AP-HP, Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Antoine Béclère, Clamart; Université Paris-Sud, Faculté de médecine, Kremlin Bicêtre, France.
David
D
Montani
INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson; AP-HP, Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Antoine Béclère, Clamart; Université Paris-Sud, Faculté de médecine, Kremlin Bicêtre, France.
Marc
M
Humbert
Service d'Anatomie Pathologique and INSERM U563, Centre Hospitalier Universitaire Purpan, Toulouse.
Pierre
P
Brousset
Service d'Explorations Fonctionnelles-Physiologie et EA 3920, Centre Hospitalier Universitaire Jean Minjoz, Besançon; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson; AP-HP, Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Antoine Béclère, Clamart. Electronic address: bruno.degano@univ-fcomte.fr.
Bruno
B
Degano
D000328:Adult; D016022:Case-Control Studies; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005602:France; D006566:Herpesviridae Infections / Q000150:complications / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000628:therapy / Q000821:virology*; D008168:Lung / Q000473:pathology / Q000821:virology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D055815:Young Adult