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on the surface of these professional antigen-presenting cells. DC-SIGN
and L-SIGN serve as antigen receptors and regulate the migration
of DCs and interaction with lymphocytes. DC-SIGN and L-SIGN
also serve as capture receptors for several microorganisms such as
human cytomegalovirus,
40
Ebola virus,
4,23
HIV-type 1,
35
Dengue virus,
102
Mycobacterium tuberclosis
,
36
and
Leishmania amastigotes
,
23
through
high mannose oligosaccharides of the pathogens.
Several groups have recently suggested that DC-SIGN and L-SIGN
are utilized as HCV receptors.
25,34,59,60,81
They demonstrated that recom-
binant E2 proteins, HCV particles derived from patient serum could
specifically bind to cells expressing DC-SIGN or L-SIGN. Although
HCV-LPs and pseudotype MLVs also efficiently bound to DCs, pre-
incubation of DCs with C-type lectins, antibodies against DC-SIGN
or DC-SIGN could not inhibit HCV-LPs binding or pseudotype
MLVs entry, suggesting that C-type lectins were not sufficient to
mediate HCV binding and entry.
7,24,44,61,81
In our previous data, pseudo-
type VSVs could enter myeloid DCs but not plasmacytoid DCs through
the interaction with lectin, however, treatment with anti-DC-SIGN
antibody did not inhibit the infection of pseudotype VSVs.
47
Therefore, DC-SIGN or L-SIGN may serve as one of the attachment
molecules of HCV but it is not clear in the entry process.
Acknowledgments
This work was supported in part by Grants-in-aid from the Ministry of
Health, Labor and Welfare, the program for Promotion of Fundamental
Studies in Health Sciences of the Organization for Drug ADR Relief,
R&D Promotion, and Product Review of Japan, the Ministry of
Education, Culture, Sports, Science and Technology, and 21st Century
Center of Excellence Program of Japan.
References
1. Acton S, Rigotti A, Landschulz KT,
et al
. (1996) Identification of scav-
enger receptor SR-BI as a high density lipoprotein receptor.
Science
271
: 518-520.
