Capture and transfer of simian immunodeficiency virus by macaque dendritic cells is enhanced by DC-SIGN.
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.
Yu Kimata
Monica T
MT
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78227, USA.
Cella
Marina
M
Biggins
Julia E
JE
Rorex
Colin
C
White
Robert
R
Hicks
Sarah
S
Wilson
Joelle M
JM
Patel
Parul G
PG
Allan
Jonathan S
JS
Colonna
Marco
M
Kimata
Jason T
JT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008254:Macaca nemestrina; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D016097:Simian Acquired Immunodeficiency Syndrome / Q000209:etiology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin