cis Expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor.
DC-SIGN is a C-type lectin expressed on dendritic cells and restricted macrophage populations in vivo that binds gp120 and acts in trans to enable efficient infection of T cells by human immunodeficiency virus type 1 (HIV-1). We report here that DC-SIGN, when expressed in cis with CD4 and coreceptors, allowed more efficient infection by both HIV and simian immunodeficiency virus (SIV) strains, although the extent varied from 2- to 40-fold, depending on the virus strain. Expression of DC-SIGN on target cells did not alleviate the requirement for CD4 or coreceptor for viral entry. Stable expression of DC-SIGN on multiple lymphoid lines enabled more efficient entry and replication of R5X4 and X4 viruses. Thus, 10- and 100-fold less 89.6 (R5/X4) and NL4-3 (X4), respectively, were required to achieve productive replication in DC-SIGN-transduced Jurkat cells when compared to the parental cell line. In addition, DC-SIGN expression on T-cell lines that express very low levels of CCR5 enabled entry and replication of R5 viruses in a CCR5-dependent manner, a property not exhibited by the parental cell lines. Therefore, DC-SIGN expression can boost virus infection in cis and can expand viral tropism without affecting coreceptor preference. In addition, coexpression of DC-SIGN enabled some viruses to use alternate coreceptors like STRL33 to infect cells, whereas in its absence, infection was not observed. Immunohistochemical and confocal microscopy data indicated that DC-SIGN was coexpressed and colocalized with CD4 and CCR5 on alveolar macrophages, underscoring the physiological significance of these cis enhancement effects.
Lee
B
B
Department of Microbiology, Immunology & Molecular Genetics, UCLA School of Medicine, Los Angeles, California 90095, USA. benhurL@microbio.ucla.edu
Leslie
G
G
Soilleux
E
E
O'Doherty
U
U
Baik
S
S
Levroney
E
E
Flummerfelt
K
K
Swiggard
W
W
Coleman
N
N
Malim
M
M
Doms
R W
RW
D015704:CD4 Antigens / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D006678:HIV / Q000502:physiology*; D006801:Humans; D037102:Lectins / Q000502:physiology*; D037181:Lectins, C-Type; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin