PMID- 16000390
OWN - NLM
STAT- MEDLINE
DCOM- 20060111
LR  - 20171116
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 78
IP  - 3
DP  - 2005 Sep
TI  - HLA-A2 down-regulation on primary human macrophages infected with an M-tropic 
      EGFP-tagged HIV-1 reporter virus.
PG  - 675-85
AB  - Multiple mechanisms are used by the human immunodeficiency virus type 1 (HIV-1) 
      to interfere with host-cell immune effector functions. The 27-kD Nef protein has 
      been shown to down-modulate specific genes of the major histocompatibility 
      complex class I (MHC-I) on the surface of infected primary T cells, facilitating 
      their escape from lysis by cytolytic T lymphocytes. Macrophages, as the other 
      major immune cell type targeted by the virus, also contribute to the 
      transmission, persistence, and pathogenesis of HIV-1. Yet, whether Nef modulates 
      MHC-I expression on HIV-infected primary macrophages remains unclear. Currently 
      available infectious HIV-1 molecular clones, which express a reporter gene, only 
      infect T cells and/or do not express Nef. To overcome these limitations, we 
      generated macrophage-tropic green fluorescent protein (GFP)-tagged HIV-1 viruses, 
      which express the complete viral genome, and used these to assess the expression 
      of human leukocyte antigen (HLA)-A2 on the surface of productively infected 
      macrophages. The reporter viral genomes were replication-competent and stable, as 
      Nef, p24 antigen, and GFP expression could be detected by immunostaining of 
      infected, monocyte-derived macrophages (MDM) after more than 2 months 
      postinfection. Fluorescence-activated cell sorter analyses of infected 
      macrophages and T cells revealed that although wild-type reporter virus infection 
      induced a statistically significant decrease in the density of surface HLA-A2, 
      down-regulation of HLA-A2 was not seen in cells infected with reporter viruses 
      encoding a frameshift or a single point mutation in Nef at prolines 74P and P80. 
      The impact of Nef on HLA-A2 surface expression in MDM was also confirmed by 
      confocal microscopy. These results suggest that the mechanisms of HLA-A2 
      down-modulation are similar in primary T cells and macrophages.
FAU - Brown, Amanda
AU  - Brown A
AD  - Department of Neurology, Meyer 6-181, 600 North Wolfe Street, Baltimore, MD 
      21287, USA. abrown76@jhmi.edu
FAU - Gartner, Suzanne
AU  - Gartner S
FAU - Kawano, Thomas
AU  - Kawano T
FAU - Benoit, Nicole
AU  - Benoit N
FAU - Cheng-Mayer, Cecilia
AU  - Cheng-Mayer C
LA  - eng
GR  - R01 AI38532/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050706
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (CD4 Antigens)
RN  - 0 (Gene Products, nef)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (enhanced green fluorescent protein)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - CD4 Antigens/immunology
MH  - Cell Line
MH  - Down-Regulation/*immunology
MH  - Gene Expression Regulation/immunology
MH  - Gene Products, nef/genetics/immunology
MH  - Green Fluorescent Proteins/biosynthesis/genetics
MH  - HIV-1/pathogenicity/*physiology
MH  - HLA-A2 Antigen/genetics/*immunology
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology/*virology
MH  - Macrophages/*immunology/virology
MH  - T-Lymphocytes/immunology/virology
MH  - Time Factors
MH  - Virus Replication
MH  - nef Gene Products, Human Immunodeficiency Virus
EDAT- 2005/07/08 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/07/08 09:00
PHST- 2005/07/08 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/07/08 09:00 [entrez]
AID - jlb.0505237 [pii]
AID - 10.1189/jlb.0505237 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2005 Sep;78(3):675-85. doi: 10.1189/jlb.0505237. Epub 2005 Jul 6.