Thrombotic microangiopathy associated with unusual viral sequences in HIV-1-positive patients

Friederike Jochimsen, Wolfram Gruening, Thierry Arnould, Mark S. Segal, Margot S. Kruskall, Robert Colgrove, Gerd Walz

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

Background. Thrombotic microangiopathy (TMA) is a rare disorder caused by endothelial cell damage. TMA has been associated with the human immunodeficiency virus 1 (HIV-1) infection, yet only a minority of all HIV-1 patients develops TMA. Since HIV-1 has been shown to interact with endothelial cells, we investigated whether certain mutations in the HIV-1 envelope protein are associated with the development of TMA in HIV-1-infected patients. Methods. Plasma was obtained from nine HIV-1-positive patients with TMA. Viral loads were determined from the samples and compared with the clinical data. Viral envelope protein sequences from the regions known to be responsible for viral tropism were isolated, sequenced and compared with known HIV-1 isolates. The isolates were expressed as synthetic fusion proteins; binding of these fusion proteins to CD4+ cells as well as to endothelial cell lines was investigated. Results. The viral loads in patients with HIV/TMA were highly variable with no correlation to the clinical status. Most patients carried macrophage-tropic viral envelope protein sequences and an unusual insertion was found in the V2 variable region. The isolates showed increased CD4 binding, but a direct binding to endothelial cells was not observed. Conclusions. Although TMA is generally diagnosed in patients with advanced HIV-1 infection, viral loads per se were not predictive of TMA in this study. While a direct interaction with endothelial cells was not detectable, specific viral envelope mutations were found in a region known to influence viral tropism. Hence, viral-specific factors might contribute to the pathogenesis of HIV-associated TMA. © ERA-EDTA 2004; all rights reserved.

langue originaleAnglais
Pages (de - à)1129-1135
Nombre de pages7
journalNephrology Dialysis Transplantation
Volume19
Numéro de publication5
Les DOIs
Etat de la publicationPublié - mai 2004

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