Expression of human herpesvirus 8 in primary pulmonary hypertension

Carlyne D. Cool, Pradeep R. Rai, Michael E. Yeager, Daniel Hernandez-Saavedra, Amanda E. Serls, Todd M. Bull, Mark W. Geraci, Kevin K. Brown, John M. Routes, Rubin M. Tuder, Norbert F. Voelkel

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1113-1122
Number of pages10
JournalNew England Journal of Medicine
Volume349
Issue number12
DOIs
StatePublished - Sep 18 2003
Externally publishedYes

Fingerprint

Human Herpesvirus 8
Pulmonary Hypertension
Cyclins
Lung
Polymerase Chain Reaction
Herpesviridae Infections
Viral Genes
Viral Antigens
Kaposi's Sarcoma
Viral Genome
Virus Diseases
Infection
Familial Primary Pulmonary Hypertension
Epigenomics
Sequence Analysis
Blood Vessels
HIV-1
Viruses
Skin
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cool, C. D., Rai, P. R., Yeager, M. E., Hernandez-Saavedra, D., Serls, A. E., Bull, T. M., ... Voelkel, N. F. (2003). Expression of human herpesvirus 8 in primary pulmonary hypertension. New England Journal of Medicine, 349(12), 1113-1122. https://doi.org/10.1056/NEJMoa035115

Expression of human herpesvirus 8 in primary pulmonary hypertension. / Cool, Carlyne D.; Rai, Pradeep R.; Yeager, Michael E.; Hernandez-Saavedra, Daniel; Serls, Amanda E.; Bull, Todd M.; Geraci, Mark W.; Brown, Kevin K.; Routes, John M.; Tuder, Rubin M.; Voelkel, Norbert F.

In: New England Journal of Medicine, Vol. 349, No. 12, 18.09.2003, p. 1113-1122.

Research output: Contribution to journalArticle

Cool, CD, Rai, PR, Yeager, ME, Hernandez-Saavedra, D, Serls, AE, Bull, TM, Geraci, MW, Brown, KK, Routes, JM, Tuder, RM & Voelkel, NF 2003, 'Expression of human herpesvirus 8 in primary pulmonary hypertension', New England Journal of Medicine, vol. 349, no. 12, pp. 1113-1122. https://doi.org/10.1056/NEJMoa035115
Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM et al. Expression of human herpesvirus 8 in primary pulmonary hypertension. New England Journal of Medicine. 2003 Sep 18;349(12):1113-1122. https://doi.org/10.1056/NEJMoa035115
Cool, Carlyne D. ; Rai, Pradeep R. ; Yeager, Michael E. ; Hernandez-Saavedra, Daniel ; Serls, Amanda E. ; Bull, Todd M. ; Geraci, Mark W. ; Brown, Kevin K. ; Routes, John M. ; Tuder, Rubin M. ; Voelkel, Norbert F. / Expression of human herpesvirus 8 in primary pulmonary hypertension. In: New England Journal of Medicine. 2003 ; Vol. 349, No. 12. pp. 1113-1122.
@article{d120780fb5014f499199173be19e0bf1,
title = "Expression of human herpesvirus 8 in primary pulmonary hypertension",
abstract = "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 = "Cool, {Carlyne D.} and Rai, {Pradeep R.} and Yeager, {Michael E.} and Daniel Hernandez-Saavedra and Serls, {Amanda E.} and Bull, {Todd M.} and Geraci, {Mark W.} and Brown, {Kevin K.} and Routes, {John M.} and Tuder, {Rubin M.} and Voelkel, {Norbert F.}",
year = "2003",
month = "9",
day = "18",
doi = "10.1056/NEJMoa035115",
language = "English (US)",
volume = "349",
pages = "1113--1122",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "12",

}

TY - JOUR

T1 - Expression of human herpesvirus 8 in primary pulmonary hypertension

AU - Cool, Carlyne D.

AU - Rai, Pradeep R.

AU - Yeager, Michael E.

AU - Hernandez-Saavedra, Daniel

AU - Serls, Amanda E.

AU - Bull, Todd M.

AU - Geraci, Mark W.

AU - Brown, Kevin K.

AU - Routes, John M.

AU - Tuder, Rubin M.

AU - Voelkel, Norbert F.

PY - 2003/9/18

Y1 - 2003/9/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0141679188&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141679188&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa035115

DO - 10.1056/NEJMoa035115

M3 - Article

C2 - 13679525

AN - SCOPUS:0141679188

VL - 349

SP - 1113

EP - 1122

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 12

ER -