The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways.
The dynamic interplay between dendritic cells (DCs) and human immunodeficiency virus type-1 (HIV-1) is thought to result in viral dissemination and evasion of antiviral immunity. Although initial observations suggested that the C-type lectin receptor (CLR) DC-SIGN was responsible for the trans-infection function of the virus, subsequent studies demonstrated that trans-infection of CD4(+) T cells with HIV-1 can also occur through DC-SIGN-independent mechanisms. We demonstrate that a cell surface molecule designated DCIR (for DC immunoreceptor), a member of a recently described family of DC-expressing CLRs, can participate in the capture of HIV-1 and promote infection in trans and in cis of autologous CD4(+) T cells from human immature monocyte-derived DCs. The contribution of DCIR to these processes was revealed using DCIR-specific siRNAs and a polyclonal antibody specific for the carbohydrate recognition domain of DCIR. Data from transfection experiments indicated that DCIR acts as a ligand for HIV-1 and is involved in events leading to productive virus infection. Finally, we show that the neck domain of DCIR is important for the DCIR-mediated effect on virus binding and infection. These results point to a possible role for DCIR in HIV-1 pathogenesis by supporting the productive infection of DCs and promoting virus propagation.
Faculté de Médecine, Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Université Laval, Québec, QC, Canada.
Alexandra A
AA
Lambert
Caroline
C
Gilbert
Manon
M
Richard
André D
AD
Beaulieu
Michel J
MJ
Tremblay
D001665:Binding Sites; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D015658:HIV Infections / Q000209:etiology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology*; D011991:Receptors, Virus; D013601:T-Lymphocytes / Q000821:virology
C423004:CLEC4A protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D011991:Receptors, Virus