Virus-Receptor Mediated Transduction of Dendritic Cells by Lentiviruses Enveloped with Glycoproteins Derived from Semliki Forest Virus

Abstract

Lentiviruses have recently attracted considerable interest for their potential as a genetic modification tool for dendritic cells (DCs). In this study, we explore the ability of lentiviruses enveloped with alphaviral envelope glycoproteins derived from Semliki Forest virus (SFV) to mediate transduction of DCs. We found that SFV glycoprotein (SFV-G)-pseudotyped lentiviruses use C-type lectins (DC-SIGN and L-SIGN) as attachment factors for transduction of DCs. Importantly, SFV-G pseudotypes appear to have enhanced transduction towards C-type lectin-expressing cells when produced under conditions limiting glycosylation to simple high-mannose, N-linked glycans. These results, in addition to the natural DC tropism of SFV-G, offer evidence to support the use of SFV-G-bearing lentiviruses to genetically modify DCs for the study of DC biology and DC-based immunotherapy.

Virus entry: old viruses, new receptors

“…Crosslinking of DC-SIGN at the cell surface by multiple high-mannose sites on the virion triggers uptake of the bound particle, resulting in antigen capture (see [29] for a recent review). DC-SIGN is used by many viruses for attachment to DCs, including MV [30], HIV-1 (see the recent review in [31]), HCV [32][33][34], Influenza A viruses [35,36], the herpes simplex virus type 1 [37], the human cytomegalovirus [38], Ebola virus [39], the SARS coronavirus [40,41], the human T-cell leukemia virus type 1 [42,43], and arboviruses belonging to the flavivirus genus -dengue virus [44,45] and west nile virus [46]) -and to the alphavirus genus, like SV [47] and aura virus [48]. In this review, we focus on recent insights for understanding the mechanism by which DC-SIGN signaling induces the uptake of the virus particle by the cell, beyond the initial attachment step.…”

Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

“…At 24 h, Johnson et al observed an increase in Langerhans cell density upon intradermal injection of wild-type SFV [ 41 ]. Despite the limited capacity of SFV to infect DCs in vitro , strategies have focused on targeting dendritic cells with the use of lentiviruses enveloped with glycoproteins derived from SFV by attaching to C-type lectins [ 42 ]. Langerhans cells may also shuttle virus particles by attachment to DC-SIGN, as observed in the case of HIV infection [ 43 ].…”

Measles Virus Glycoprotein-Pseudotyped Lentiviral Vectors Are Highly Superior to Vesicular Stomatitis Virus G Pseudotypes for Genetic Modification of Monocyte-Derived Dendritic Cells

“…In accordance with these data, we demonstrated that DC-SIGN plays a role in the high-level transduction of MDDCs by H/F-LVs. Interestingly, DC-SIGN appears to be targeted by multiple native viruses (36), and it was used as a major DC specific target receptor for redirecting LV vector tropism both in vitro and in vivo, i.e., mainly dermal DCs (31,32,63,89). In addition, DC-SIGN has been shown to mediate suppression of innate immune responses via the TLR-dependent expression of the regulatory cytokine IL-10 by DCs (44,45).…”