NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi's sarcoma

Maria Caterina Sirianni, Laura Vincenzi, Simone Topino, Antonello Giovannetti, Francesca Mazzetta, Fabio Libi, Donato Scaramuzzi, Massimo Andreoni, Elena Pinter, Sara Baccarini, Giovanni Rezza, Paolo Monini, Barbara Ensoli

Research output: Contribution to journalArticlepeer-review

Abstract

Kaposi's sarcoma (KS) develops upon reactivation of human herpesvirus 8 (HHV8) infection and virus dissemination to blood and tissue cells, including endothelial and KS spindle cells where the virus is mostly present in a latent form. However, this may likely require the presence of compromised host immune responses and/or the evasion of infected cells from the host immune response. In this regard, mechanisms of evasion of productively infected cells from both CTL and NK cell responses, and resistance of latently infected cells from specific CTL, have already been shown. Here we show that cells which are latently infected by HHV8 are indeed efficiently lysed by NK cells from individuals with a normal immune response. Notably, NK cell-mediated immunity was found to be significantly reduced in AIDS patients with progressing KS as compared to both HIV-negative patients with indolent classic KS or normal blood donors. However, it was restored after treatment with the highly active antiretroviral therapy (HAART) in AIDS-KS patients, that showed regression and clearance of HHV8 from PBMC. By contrast, AIDS-KS patients with a more aggressive disease and no clinical response had persistent HHV8 viremia associated with reduced NK cell cytotoxicity. These results suggest a key role for NK cells in the control of HHV8 latent infection, KS development, and in disease remission upon HAART.

Original languageEnglish
Pages (from-to)2711-2720
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 2002

Keywords

  • Highly active antiretroviral therapy
  • Kaposi's sarcoma
  • Kaposi's sarcoma-associated herpesvirus
  • NK cell

ASJC Scopus subject areas

  • Immunology

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