| Title | Capture and transfer of simian immunodeficiency virus by macaque dendritic cells is enhanced by DC-SIGN. | | Author(s) | Yu Kimata MT, Cella M, Biggins JE, Rorex C, White R, Hicks S, Wilson JM, Patel PG, Allan JS, Colonna M, Kimata JT | | Institution | Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227, USA. | | Source | J Virol 2002 Dec; 76(23):11827-36. | | MeSH | Animals
Antibodies, Monoclonal
Binding Sites
CD4-Positive T-Lymphocytes
Cell Adhesion Molecules
Cell Line
Dendritic Cells
HIV-1
Humans
Lectins, C-Type
Macaca nemestrina
Receptors, Cell Surface
Research Support, U.S. Gov't, P.H.S.
Sequence Deletion
Simian Acquired Immunodeficiency Syndrome
Simian immunodeficiency virus
| | Abstract | Dendritic cells (DCs) are among the first cells encountered by human and simian immunodeficiency virus (HIV and SIV) following mucosal infection. Because these cells efficiently capture and transmit virus to T cells, they may play a major role in mediating HIV and SIV infection. Recently, a C-type lectin protein present on DCs, DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), was shown to efficiently bind and present HIV and SIV to CD4(+), coreceptor-positive cells in trans. However, the significance of DC-SIGN for virus transmission and pathogenesis in vivo remains unclear. Because SIV infection of macaques may represent the best model to study the importance of DC-SIGN in HIV infection, we cloned and characterized pig-tailed macaque DC-SIGN and generated monoclonal antibodies (MAbs) against it. We demonstrate that, like human DC-SIGN, pig-tailed macaque DC-SIGN (ptDC-SIGN) is expressed on DCs and macrophages but not on monocytes, T cells, or B cells. Moderate levels of ptDC-SIGN expression were detected on the surface of DCs, and low-level expression was found on macrophages. Additionally, we show that ptDC-SIGN efficiently binds and transmits replication-competent SIVmne variants to CD4(+), coreceptor-positive cells. Moreover, transmission of virus between pig-tailed macaque DCs and CD4(+) T cells is largely ptDC-SIGN dependent. Interestingly, MAbs directed against ptDC-SIGN vary in the capacity to block transmission of different SIVmne variants. These data demonstrate that ptDC-SIGN plays a central role in transmitting virus from macaque DCs to T cells, and they suggest that SIVmne variants may differ in their interactions with ptDC-SIGN. Thus, SIVmne infection of pig-tailed macaques may provide an opportunity to investigate the significance of DC-SIGN in primate lentiviral infections. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12414925 |
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