Usage of Integrin and Heparan Sulfate as Receptors for Mouse Adenovirus Type 1

Raman, Sharmila; Hsu, Tien; Ashley, Shanna L.; Spindler, Katherine R.

doi:10.1128/jvi.02368-08

Cited by 18 publications

(21 citation statements)

References 65 publications

(76 reference statements)

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“…It is possible that certain non-RGD containing AdV serotypes (e.g., HAdV-40 and -41) either do not use the vitronectin-binding integrins for infection or that they use distinct receptors, as has been suggested from earlier studies (Chillon and Kremer 2001). Recently, an integrin-binding RGD sequence was identified in the fiber protein of MAdV-1, further underscoring the importance of integrin interactions in AdV entry (Raman et al 2009). Deletion or mutation of the RGD sequence in recombinant HAdV-5 vectors results in diminished virus infection in vitro as well as in vivo (Bai et al 1993; Einfeld et al 2001; Goldman and Wilson 1995).…”

Section: Adenovirus Internalizationmentioning

confidence: 99%

Adenovirus

Smith

Wiethoff

Stewart

et al. 2010

Current Topics in Microbiology and Immunology

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Of the 53 different human adenovirus (HAdV) serotypes belonging to species A-G, a significant number are associated with acute respiratory, gastrointestinal and ocular infections. Replication-defective HAdV-5-based vectors also continue to play a significant role in gene transfer trials and in vaccine delivery efforts in the clinic. Although significant progress has been made from studies of AdV biology, we still have an incomplete understanding of AdV’s structure as well as its multifactorial interactions with the host. Continuing efforts to improve knowledge in these areas, as discussed in this chapter, will be crucial for revealing the mechanisms of AdV pathogenesis and for allowing optimal use of AdV vectors for biomedical applications.

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Section: Adenovirus Internalizationmentioning

confidence: 99%

Adenovirus

Smith

Wiethoff

Stewart

et al. 2010

Current Topics in Microbiology and Immunology

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“…In infected mice with advanced disease, MAV-1 is typically found in the endothelial cells of infected organs [18], [19]. A previous investigation pointed to a role for HSPGs and α V integrins in the MAV-1 infection cycle, however it was not determined whether HSPGs are implicated in cellular attachment or, rather, entry of MAV-1 into susceptible cells [20]. In this study, we focused on the involvement of cell membrane HSPGs in the initial attachment of MAV-1, and examined the role of specific N- or O-sulfate groups in the HSPGs.…”

Section: Introductionmentioning

confidence: 99%

Interaction between Mouse Adenovirus Type 1 and Cell Surface Heparan Sulfate Proteoglycans

et al. 2012

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Application of human adenovirus type 5 (Ad5) derived vectors for cancer gene therapy has been limited by the poor cell surface expression, on some tumor cell types, of the primary Ad5 receptor, the coxsackie-adenovirus-receptor (CAR), as well as the accumulation of Ad5 in the liver following interaction with blood coagulation factor X (FX) and subsequent tethering of the FX-Ad5 complex to heparan sulfate proteoglycan (HSPG) on liver cells. As an alternative vector, mouse adenovirus type 1 (MAV-1) is particularly attractive, since this non-human adenovirus displays pronounced endothelial cell tropism and does not use CAR as a cellular attachment receptor. We here demonstrate that MAV-1 uses cell surface heparan sulfate proteoglycans (HSPGs) as primary cellular attachment receptor. Direct binding of MAV-1 to heparan sulfate-coated plates proved to be markedly more efficient compared to that of Ad5. Experiments with modified heparins revealed that the interaction of MAV-1 to HSPGs depends on their N-sulfation and, to a lesser extent, 6-O-sulfation rate. Whereas the interaction between Ad5 and HSPGs was enhanced by FX, this was not the case for MAV-1. A slot blot assay demonstrated the ability of MAV-1 to directly interact with FX, although the amount of FX complexed to MAV-1 was much lower than observed for Ad5. Analysis of the binding of MAV-1 and Ad5 to the NCI-60 panel of different human tumor cell lines revealed the preference of MAV-1 for ovarian carcinoma cells. Together, the data presented here enlarge our insight into the HSPG receptor usage of MAV-1 and support the development of an MAV-1-derived gene vector for human cancer therapy.

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“…MAdV-1 lacks the RGD motif in the penton base, but it contains it in the fiber knob domain (Raman et al, 2009). The RGD motif was reported to play a role in MAdV-1 infection through a v integrins, which act as a receptor for the virus, and it was shown that cell surface heparan sulfate glycosaminoglycans are involved in MAdV-1 infection (Raman et al, 2009). Conversely, the primary attachment of MAdV-1 is independent of CAR (Lenaerts et al, 2006).…”

Section: Murine Adv Vectorsmentioning

confidence: 96%

“…MAdV-1 presents mouse endothelial cell tropism (Charles et al, 1998;Kajon et al, 1998;Lenaerts et al, 2005), but it can also infect human endothelial cells (Nguyen et al, 1999) and it displays higher affinity for primary human smooth muscle cells than recombinant HAdV-5 (Lenaerts et al, 2009). MAdV-1 lacks the RGD motif in the penton base, but it contains it in the fiber knob domain (Raman et al, 2009). The RGD motif was reported to play a role in MAdV-1 infection through a v integrins, which act as a receptor for the virus, and it was shown that cell surface heparan sulfate glycosaminoglycans are involved in MAdV-1 infection (Raman et al, 2009).…”

Section: Murine Adv Vectorsmentioning

confidence: 97%

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

et al. 2014

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Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles.

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Usage of Integrin and Heparan Sulfate as Receptors for Mouse Adenovirus Type 1

Cited by 18 publications

References 65 publications

Adenovirus

Adenovirus

Interaction between Mouse Adenovirus Type 1 and Cell Surface Heparan Sulfate Proteoglycans

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

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