Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR.
The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)] bind and transmit human immunodeficiency virus (HIV) and simian immunodeficiency virus to T cells via the viral envelope glycoprotein (Env). Other viruses containing heavily glycosylated glycoproteins (GPs) fail to interact with DC-SIGN(R), suggesting some degree of specificity in this interaction. We show here that DC-SIGN(R) selectively interact with HIV Env and Ebola virus GPs containing more high-mannose than complex carbohydrate structures. Modulation of N-glycans on Env or GP through production of viruses in different primary cells or in the presence of the mannosidase I inhibitor deoxymannojirimycin dramatically affected DC-SIGN(R) infectivity enhancement. Further, murine leukemia virus, which typically does not interact efficiently with DC-SIGN(R), could do so when produced in the presence of deoxymannojirimycin. We predict that other viruses containing GPs with a large proportion of high-mannose N-glycans will efficiently interact with DC-SIGN(R), whereas those with solely complex N-glycans will not. Thus, the virus-producing cell type is an important factor in dictating both N-glycan status and virus interactions with DC-SIGN(R), which may impact virus tropism and transmissibility in vivo.
Lin
George
G
Hematology-Oncology Division, Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Simmons
Graham
G
Pöhlmann
Stefan
S
Baribaud
Frédéric
F
Ni
Houping
H
Leslie
George J
GJ
Haggarty
Beth S
BS
Bates
Paul
P
Weissman
Drew
D
Hoxie
James A
JA
Doms
Robert W
RW
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D029043:Ebolavirus / Q000378:metabolism*; D006031:Glycosylation; D006678:HIV / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human