The importance of coagulation factors binding to adenovirus: historical perspectives and implications for gene delivery

Lopez-Gordo, Estrella; Denby, Laura; Nicklin, Stuart A.; Baker, Andrew H.

doi:10.1517/17425247.2014.938637

Cited by 21 publications

(28 citation statements)

References 166 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And, enhancement of HIV-1 infection by human α-defensins HD5 and HD6 is also independent of CD4 and co-receptors [26]. For HAdVs in particular, an analogous mechanism governs liver and spleen cell tropism via blood coagulation factors that bind to hexon and bridge interactions with heparin sulfate proteoglycans on the cell surface [36]. Alternatively, some mouse α-defensins can permeabilize eukaryotic membranes [37], perhaps leading to increased infection by forming pores at the cell surface or facilitating disruption of the endosomal membrane, resulting in more virus reaching the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Alpha-defensin-dependent enhancement of enteric viral infection

et al. 2017

View full text Add to dashboard Cite

The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. Although they most commonly function as potent antivirals in cell culture, enteric α-defensins have also been shown to enhance some viral infections in vitro. Efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. To address this issue, here we use primary stem cell-derived small intestinal enteroids to examine the impact of naturally secreted α-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2). MAdV-2 infection was increased when enteroids were inoculated across an α-defensin gradient in a manner that mimics oral infection but not when α-defensin levels were absent or bypassed through other routes of inoculation. This increased infection was a result of receptor-independent binding of virus to the cell surface. The enteroid experiments accurately predicted increased MAdV-2 shedding in the feces of wild type mice compared to mice lacking functional α-defensins. Thus, our studies have shown that viral infection enhanced by enteric α-defensins may reflect the evolution of some viruses to utilize these host proteins to promote their own infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Alpha-defensin-dependent enhancement of enteric viral infection

et al. 2017

View full text Add to dashboard Cite

show abstract

“…), their biodistribution is heavily influenced by blood proteins that bind to (opsonize) the vector (1). Natural antibodies and complement increase clearance of vector by Kupffer cells (KCs) (2), while coagulation factor X (FX) increases transduction of hepatocytes by vector (3)(4)(5).…”

mentioning

confidence: 99%

Impact of Natural IgM Concentration on Gene Therapy with Adenovirus Type 5 Vectors

Qiu

Tian

et al. 2015

J Virol

View full text Add to dashboard Cite

“…It is known that liver sequestration of human adenovirus serotype 5 (Ad5) limits therapeutic efficacy. Recent findings suggest that interactions of Ad5 capsid protein, hexon, with the blood coagulation factor X (FX) lead these complexes to attach to cell surface heparin sulfate proteoglycans (HSPGs) on hepatocytes [22,24,26]. The attachment of this complex causes sequestration of adenoviral therapeutic vehicles on liver [22,24].…”

Section: Hexon-modified Adenoviral Vaccine Mediates Superior Vaccine mentioning

confidence: 99%

“…For example, most people have neutralizing antibodies (NAb) against Ad5, especially the fiber (i.e., the most structurally protruding viral domain) and the hexon (most structurally abundant domain) [21,22]. In addition to this immune-mediated vector clearance, it is known that systemic delivery of adenovirus can cause liver sequestration and toxicity due to the interaction between coagulation factor X (FX) and the adenoviral hexon protein [23][24][25][26]. To overcome the first obstacle of NAb against the fiber domain, we modified the structurally exposed fiber domain with the scFvDEC205 and incorporated this into a chimeric fiber fibritin structure, which originates from bacteriophage (Sup Fig 1).…”

Section: Introductionmentioning

confidence: 99%

“…To overcome the first obstacle of NAb against the fiber domain, we modified the structurally exposed fiber domain with the scFvDEC205 and incorporated this into a chimeric fiber fibritin structure, which originates from bacteriophage (Sup Fig 1). Secondly, to minimize liver sequestration and the recognition of NAbs against the viral hexon, we replaced the hexon domain of Ad5 with that of human Ad serotype 3 (Ad3), since it has been shown the hexon of Ad3 has relatively low affinity to FX, and this serotype 3 is less prevalent in humans, making pre-existing NAb formation less likely [23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model

Kim¹,

Kane²,

Panek³

et al. 2018

Neurotherapeutics

View full text Add to dashboard Cite

Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body's most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261-implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.

show abstract

The importance of coagulation factors binding to adenovirus: historical perspectives and implications for gene delivery

Cited by 21 publications

References 166 publications

Alpha-defensin-dependent enhancement of enteric viral infection

Alpha-defensin-dependent enhancement of enteric viral infection

Impact of Natural IgM Concentration on Gene Therapy with Adenovirus Type 5 Vectors

A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model

Contact Info

Product

Resources

About