ncreasing lines of evidence indicate that NKG2D, an activating receptor of natural killer (NK) and CD8(+) T cells, plays an important role in immune responses against HIV-1. Through its ability to recognize a diverse array of ligands (NKG2DLs) induced by cell 'stress' such as viral infection, NKG2D delivers activating and co-stimulatory signals resulting in cytotoxicity and release of cytokines. Therefore, HIV-1 and other viruses have evolved clever mechanisms to counteract NKG2D-dependent immune responses. While, on one hand, the HIV-1 Vpr protein up-regulates NKG2DLs expression by activating the DNA damage response (DDR) pathway, other viral proteins (Nef and Vif) have developed the capacity to reduce NKG2DLs expression levels. In addition, recent evidences suggest that HIV-1-infected CD4(+) T cells may release NKG2DLs, particularly MICA, in soluble form, a phenomenon that has the potential to down-modulate NKG2D on circulating lymphocytes and allow evasion of NKG2D-mediated immune responses. Indeed, despite controversial, lower NKG2D expression was found on both NK and CD8(+) T cells in HIV-1-infected patients. This review discusses recent advances in the understanding of how HIV-1 affects the NKG2D/NKG2DLs system, with a special focus on virus-induced release of soluble NKG2DLs and its functional implications for the immune surveillance of the infected host.

Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1? / Giuliani, Rica; Vassena, Lia; Cerboni, Cristina; Doria, Margherita. - In: CURRENT DRUG TARGETS. - ISSN 1389-4501. - STAMPA. - 17:(2016), pp. 54-64. [10.2174/1389450116666150630110329]

Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1?

CERBONI, CRISTINA;
2016

Abstract

ncreasing lines of evidence indicate that NKG2D, an activating receptor of natural killer (NK) and CD8(+) T cells, plays an important role in immune responses against HIV-1. Through its ability to recognize a diverse array of ligands (NKG2DLs) induced by cell 'stress' such as viral infection, NKG2D delivers activating and co-stimulatory signals resulting in cytotoxicity and release of cytokines. Therefore, HIV-1 and other viruses have evolved clever mechanisms to counteract NKG2D-dependent immune responses. While, on one hand, the HIV-1 Vpr protein up-regulates NKG2DLs expression by activating the DNA damage response (DDR) pathway, other viral proteins (Nef and Vif) have developed the capacity to reduce NKG2DLs expression levels. In addition, recent evidences suggest that HIV-1-infected CD4(+) T cells may release NKG2DLs, particularly MICA, in soluble form, a phenomenon that has the potential to down-modulate NKG2D on circulating lymphocytes and allow evasion of NKG2D-mediated immune responses. Indeed, despite controversial, lower NKG2D expression was found on both NK and CD8(+) T cells in HIV-1-infected patients. This review discusses recent advances in the understanding of how HIV-1 affects the NKG2D/NKG2DLs system, with a special focus on virus-induced release of soluble NKG2DLs and its functional implications for the immune surveillance of the infected host.
2016
MICA, MICB, NKG2D, shedding, ULBP1-6, HIV-1
01 Pubblicazione su rivista::01a Articolo in rivista
Release of Soluble Ligands for the Activating NKG2D Receptor: One More Immune Evasion Strategy Evolved by HIV-1? / Giuliani, Rica; Vassena, Lia; Cerboni, Cristina; Doria, Margherita. - In: CURRENT DRUG TARGETS. - ISSN 1389-4501. - STAMPA. - 17:(2016), pp. 54-64. [10.2174/1389450116666150630110329]
File allegati a questo prodotto
File Dimensione Formato  
Giuliani_Realase_2016.pdf

accesso aperto

Note: Articolo principale
Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 316.04 kB
Formato Adobe PDF
316.04 kB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/907777
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 5
social impact