PMID- 17170457
OWN - NLM
STAT- MEDLINE
DCOM- 20070227
LR  - 20201215
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 88
IP  - Pt 1
DP  - 2007 Jan
TI  - Human immunodeficiency virus 1 Nef protein downmodulates the ligands of the 
      activating receptor NKG2D and inhibits natural killer cell-mediated cytotoxicity.
PG  - 242-250
LID - 10.1099/vir.0.82125-0 [doi]
AB  - 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.
FAU - Cerboni, Cristina
AU  - Cerboni C
AD  - Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione 
      Cenci Bolognetti, University La Sapienza, 00161 Rome, Italy.
FAU - Neri, Francesca
AU  - Neri F
AD  - Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesu, 
      Piazza S. Onofrio 4, 00165 Rome, Italy.
FAU - Casartelli, Nicoletta
AU  - Casartelli N
AD  - Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesu, 
      Piazza S. Onofrio 4, 00165 Rome, Italy.
FAU - Zingoni, Alessandra
AU  - Zingoni A
AD  - Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione 
      Cenci Bolognetti, University La Sapienza, 00161 Rome, Italy.
FAU - Cosman, David
AU  - Cosman D
AD  - Amgen, Seattle, WA 98101, USA.
FAU - Rossi, Paolo
AU  - Rossi P
AD  - Department of Pediatrics, University Tor Vergata, 00133 Rome, Italy.
AD  - Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesu, 
      Piazza S. Onofrio 4, 00165 Rome, Italy.
FAU - Santoni, Angela
AU  - Santoni A
AD  - Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione 
      Cenci Bolognetti, University La Sapienza, 00161 Rome, Italy.
FAU - Doria, Margherita
AU  - Doria M
AD  - Division of Immunology and Infectious Disease, Children's Hospital Bambino Gesu, 
      Piazza S. Onofrio 4, 00165 Rome, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Gene Products, nef)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (Ligands)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Natural Killer Cell)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Cell Line
MH  - Cytotoxicity, Immunologic
MH  - Down-Regulation/drug effects/immunology
MH  - Gene Products, nef/*pharmacology
MH  - HIV-1/*chemistry/immunology
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Ligands
MH  - NK Cell Lectin-Like Receptor Subfamily K
MH  - Receptors, Immunologic/*metabolism
MH  - Receptors, Natural Killer Cell
MH  - nef Gene Products, Human Immunodeficiency Virus
EDAT- 2006/12/16 09:00
MHDA- 2007/02/28 09:00
CRDT- 2006/12/16 09:00
PHST- 2006/12/16 09:00 [pubmed]
PHST- 2007/02/28 09:00 [medline]
PHST- 2006/12/16 09:00 [entrez]
AID - 10.1099/vir.0.82125-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2007 Jan;88(Pt 1):242-250. doi: 10.1099/vir.0.82125-0.