APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection.
HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA-mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5alpha, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.
Pion
Marjorie
M
Department of Dermatology and Venereology, University Hospital and Medical School of Geneva, 1211 Geneva, Switzerland.
Granelli-Piperno
Angela
A
Mangeat
Bastien
B
Stalder
Romaine
R
Correa
Rafael
R
Steinman
Ralph M
RM
Piguet
Vincent
V
D000071480:APOBEC-3G Deaminase; D000090103:Antiviral Restriction Factors; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D005434:Flow Cytometry; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology*; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017354:Point Mutation; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014759:Viral Envelope Proteins / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D004279:DNA, Viral; C028391:G protein, vesicular stomatitis virus; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000070584:Tripartite Motif Proteins; D014759:Viral Envelope Proteins; D049452:Green Fluorescent Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D009700:Nucleoside Deaminases; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase