Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity

Cristina Cerboni, Francesca Neri, Nicoletta Casartelli, Alessandra Zingoni, David Cosman, Paolo Rossi, Angela Santoni, Margherita Doria

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Natural killer (NK) cells are a major component of the host innate immune defence against various pathogens. Several viruses, including Human immunodeficiency virus 1 (HIV-1), have developed strategies to evade the NK-cell response. This study was designed to evaluate whether HIV-1 could interfere with the expression of NK cell-activating ligands, specifically the human leukocyte antigen (HLA)-I-like MICA and ULBP molecules that bind NKG2D, an activating receptor expressed by all NK cells. Results show that the HIV-1 Nef protein downmodulates cell-surface expression of MICA, ULBP1 and ULBP2, with a stronger effect on the latter molecule. The activity on MICA and ULBP2 is well conserved in Nef protein variants derived from HIV-1-infected patients. In HIV-1-infected cells, cell-surface expression of NKG2D ligands increased to a higher extent with a Nef-deficient virus compared with wild-type virus. Mutational analysis of Nef showed that NKG2D ligand downmodulation has structural requirements that differ from those of other reported Nef activities, including HLA-I downmodulation. Finally, data demonstrate that Nef expression has functional consequences on NK-cell recognition, causing a decreased susceptibility to NK cell-mediated lysis. These findings provide a novel insight into the mechanisms evolved by HIV-1 to escape from the NK-cell response.

Original languageEnglish
Pages (from-to)242-250
Number of pages9
JournalJournal of General Virology
Volume88
Issue number1
DOIs
Publication statusPublished - Jan 2007

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NK Cell Lectin-Like Receptor Subfamily K
Natural Killer Cells
Ligands
HIV-1
HLA Antigens
Viruses
nef Gene Products
Human immunodeficiency virus 1 nef protein

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity. / Cerboni, Cristina; Neri, Francesca; Casartelli, Nicoletta; Zingoni, Alessandra; Cosman, David; Rossi, Paolo; Santoni, Angela; Doria, Margherita.

In: Journal of General Virology, Vol. 88, No. 1, 01.2007, p. 242-250.

Research output: Contribution to journalArticle

Cerboni, Cristina ; Neri, Francesca ; Casartelli, Nicoletta ; Zingoni, Alessandra ; Cosman, David ; Rossi, Paolo ; Santoni, Angela ; Doria, Margherita. / Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity. In: Journal of General Virology. 2007 ; Vol. 88, No. 1. pp. 242-250.
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