Mouse adenovirus type 1 and human adenovirus type 5 differ in endothelial cell tropism and liver targeting

Lenaerts, Liesbeth; McVey, John H.; Baker, Andrew H.; Denby, Laura; Nicklin, Stuart A.; Verbeken, Erik; Naesens, Lieve

doi:10.1002/jgm.1283

Cited by 12 publications

(14 citation statements)

References 38 publications

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“…It will be of interest to determine whether MAV-1 interaction with HS-GAGs is direct or mediated by soluble factors. Recent surface plasmon resonance experiments by Lenaerts et al demonstrated that MAV-1 binds to mouse factors IX and X (35). However, the addition of factor X at physiologic concentrations did not increase the attachment of MAV-1 to mouse hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Also, mCAR mRNA is not expressed in some mouse cell lines (55) that we have found are productively infected by MAV-1 (K. R. Spindler, unpublished data). MAV-1 has recently been shown to associate with mouse coagulation factors IX and X, but this does not lead to enhanced cellular attachment to hepatocytes (35). It is not known what MAV-1 uses as attachment and/or internalization receptors.…”

mentioning

confidence: 99%

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

Raman

Hsu

Ashley

et al. 2009

J Virol

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Raman

Hsu

Ashley

et al. 2009

J Virol

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“…Interestingly, species differences in the levels of FX-mediated transduction efficacy of HAd5 mediated via heparan sulfates have been also reported for mouse and human FX (56,57). Furthermore, HAd5 and mouse adenovirus type 1 (MAd1) differ in their FX binding-dependent tropisms in the mouse model (58). While these differences do not exclude the possibility of TLR4-dependent recognition of mFXcomplexed MAd1, they imply different steric orientations of mouse FX and human FX on different capsids.…”

Section: Discussionmentioning

confidence: 99%

Human Coagulation Factor X-Adenovirus Type 5 Complexes Poorly Stimulate an Innate Immune Response in Human Mononuclear Phagocytes

Eichholz

Mennechet

Kremer

2015

J Virol

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One of the first lines of host defense against many viruses in vertebrates is the innate immune system, which detects pathogenassociated molecular patterns (PAMPs) using pathogen recognition receptors (PRR). The dynamic interactions between pathogens and hosts create, in some cases, species-specific relationships. Recently, it was shown that murine factor X (mFX)-armored human adenovirus (HAd) stimulated a mFX-Toll-like receptor 4 (TLR4)-associated response in mouse macrophages in vitro and in vivo. Given the importance of studies using animals to better understand host-pathogen interactions, we asked if human FX (hFX)-armored HAd type 5 (HAd5) was capable of activating innate immune sensors in primary human mononuclear phagocytes. To this end, we assayed human mononuclear phagocytes for their ability to be stimulated by hFX-armored HAd5 via a TLR/NF-B pathway, in particular, a TLR4 pathway. In our hands, we found no significant interaction, activation, or maturation of human mononuclear phagocytes caused by the presence of hFX-armored HAd5. IMPORTANCEAnimals, and mice in particular, are often used as informative and powerful surrogates for how pathogens interact with natural host systems. When possible, extended and targeted studies in the natural host can then be performed. Our data will help us understand the differences in preclinical testing in mice and clinical use in humans in order to improve treatment for HAd diseases and Ad vector effectiveness. The innate response uses an array of pathogen recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs). The best-characterized PRRs are the members of the Toll-like receptor family (TLRs); among them, TLR4 is arguably the most studied. Due to the endemic and occasional epidemic nature of human adenovirus (HAd) infections, and the advent of human and nonhuman Ad-derived vectors for shortterm (e.g., vaccines) and long-term (e.g., brain gene transfer) (1, 2) transgene expression, understanding their interaction with the innate immune system is fundamental to better treat HAd diseases and to optimize the efficacy of gene transfer vectors. Studies addressing the interaction of HAds with PRR have demonstrated that these pathogens trigger signals from cytosolic-and/or vesiclecompartmentalized double-stranded DNA sensors (3-6).Wild-type and transgenic mice are commonly used to assess the risk and efficacy of drugs and treatments and have been valuable models from which many paradigms of immunology have been derived. Although there are differences that affect the transcriptional response and functionality of several leukocyte lineages (7, 8) and TLR4 signaling (9), there are many features conserved between human and murine immune systems. Yet a recent pair of studies described contrasting interpretations-using the same data set-of the fidelity of mouse models with respect to mimicking human inflammatory diseases (59, 60).When pathogens are concerned, the results generated in mice can influence therapies in humans. The interaction bet...

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“…Conversely, the primary attachment of MAdV-1 is independent of CAR (Lenaerts et al, 2006). Distribution of MAdV-1 to the liver is markedly lower in intravenously injected immunodeficient mice than that observed with recombinant HAdV-5 (Lenaerts et al, 2009). Moreover, MAdV-1 has been used as an oncolytic vector, proving that it is a suitable murine homolog model to test the mechanism of action of murine oncolytic AdV vectors in an immunocompetent, tumor-bearing host (Robinson et al, 2009).…”

Section: Murine Adv Vectorsmentioning

confidence: 93%

“…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).…”

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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Mouse adenovirus type 1 and human adenovirus type 5 differ in endothelial cell tropism and liver targeting

Abstract: Our data on the tropism of MAV-1 suggest that this virus may find utility in the field of gene therapy.

Cited by 12 publications

References 38 publications

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

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

Human Coagulation Factor X-Adenovirus Type 5 Complexes Poorly Stimulate an Innate Immune Response in Human Mononuclear Phagocytes

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

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