Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

doi:10.1073/pnas.032654399

Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

^*HIV Drug Resistance Program, ^†Laboratory of Genomic Diversity, and ^¶Basic Research Program, Science Applications International Corporation Frederick, National Cancer Institute, Frederick, MD 21702; ^‡Population Council, Center for Biomedical Research, New York, NY 10021; and ^§Vanderbilt University, School of Medicine, Nashville, TN 37232

Communicated by John M. Coffin, Tufts University School of Medicine, Boston, MA (received for review October 19, 2001)

Abstract

Here, we describe the isolation and characterization of the rhesus macaque homolog for human DC-SIGN, a dendritic cell-specific C-type lectin. mac-DC-SIGN is 92% identical to hu-DC-SIGN. mac-DC-SIGN preserves the virus transmission function of hu-DC-SIGN, capturing and efficiently transducing simian and human immunodeficiency virus to target CD4⁺ T cells. Surprisingly, however, mac-DC-SIGN plays no discernable role in the ability of rhesus macaque dendritic cells to capture and transmit primate lentiviruses. Expression and neutralization analyses suggest that this process is DC-SIGN independent in macaque, although the participation of other lectin molecules cannot be ruled out. The ability of primate lentiviruses to effectively use human and rhesus dendritic cells in virus transmission without the cells becoming directly infected suggests that these viruses have taken advantage of a conserved dendritic cell mechanism in which DC-SIGN family molecules are significant contributors but not the only participants.

Footnotes

↵ ‖ To whom reprint requests should be addressed. E-mail: vineet{at}ncifcrf.gov.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY040319).
Abbreviations:

DC,

dendritic cell(s);

ICAM-3,

intercellular adhesion molecule 3;

hu-DC-SIGN,

human DC-specific ICAM-3-grabbing nonintegrin;

mac-DC-SIGN,

rhesus macaque DC-SIGN;

Env,

envelope;

FACS,

fluorescence-activated cell sorter;

PBMC,

peripheral blood mononuclear cells;

SIV,

simian immunodeficiency virus;

CCR,

CC chemokine receptor