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Journal of Virology, January 2003, p. 1337-1346, Vol. 77, No. 2
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.2.1337-1346.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Hematology-Oncology Division, Department of Medicine,1 Department of Microbiology,2 Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania 191043
Received 8 July 2002/ Accepted 27 September 2002
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.
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