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.
Lambert
Alexandra A
AA
Faculté de Médecine, Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Université Laval, Québec, QC, Canada.
Gilbert
Caroline
C
Richard
Manon
M
Beaulieu
André D
AD
Tremblay
Michel J
MJ
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