Adams WC, Bond E, Havenga MJ et al.Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus-adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN. J Gen Virol 90:1600-1610

Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Journal of General Virology (Impact Factor: 3.18). 04/2009; 90(Pt 7):1600-10. DOI: 10.1099/vir.0.008342-0
Source: PubMed


The coxsackievirus-adenovirus receptor (CAR) is the described primary receptor for adenovirus serotype 5 (Ad5), a common human pathogen that has been exploited as a viral vector for gene therapy and vaccination. This study showed that monocytes and dendritic cells (DCs), such as freshly isolated human blood myeloid DCs, plasmacytoid DCs and monocyte-derived DCs, are susceptible to recombinant Ad5 (rAd5) infection despite their lack of CAR expression. Langerhans cells and dermal DCs from skin expressed CAR, but blocking CAR only partly decreased rAd5 infection, together suggesting that other receptor pathways mediate viral entry of these cells. Lactoferrin (Lf), an abundant protein in many bodily fluids known for its antiviral and antibacterial properties, promoted rAd5 infection in all cell populations except plasmacytoid DCs using a CAR-independent process. Lf caused phenotypic differentiation of the DCs, but cell activation played only a minor role in the increase in infection frequencies. The C-type lectin receptor DC-SIGN facilitated viral entry of rAd5-Lf complexes and this was dependent on high-mannose-type N-linked glycans on Lf. These results suggest that Lf present at high levels at mucosal sites can facilitate rAd5 attachment and enhance infection of DCs. A better understanding of the tropism and receptor mechanisms of Ad5 may help explain Ad5 pathogenesis and guide the engineering of improved rAd vectors.

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    • "Use of lipofectamine has been reported to improve the transduction efficiency of human hematopoietic stem cells (Byk et al., 1998). Lactoferrin can be used as a bridge to enhance binding between the host cell and the virus to increase transduction efficiency (Adams et al., 2009). "
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    • "Additionally, higher levels of transcripts for antimicrobial molecules such as cathelicidin (Camp) (section XI Table 1) and lactotransferrin (Ltf) (section XII Table 1) were detected. Human cathelicidin has been reported to inactivate adenoviruses [14] and lactotransferrin to mediate entry of adenovirus subtype 5 virus into cells [15]. The only chemokine-related genes more highly expressed in spleen i.d. "
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    • "Huang et al demonstrated that adenovirus binds to hematopoietic cells via a penton base interaction with Integrin αMβ2, an integrin not expressed on epithelial cells, but still requires αv integrins for virus internalization [13]. Additionally, Ad5 has also been proposed to use heparan sulphate glycosaminoglycans as receptors [14,15] and to use lactoferrin as a bridge between viral particles and the cell surface [16,17]. In both of these systems, adenovirus fiber is the viral protein required for binding. "
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