General analysis of receptor-mediated viral attachment to cell surfaces

Wickham, Thomas J.; Granados, Robert R.; Wood, Helen; Hammer, Daniel A.; Shuler, Michael L.

doi:10.1016/s0006-3495(90)82495-4

Cited by 101 publications

(77 citation statements)

References 51 publications

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“…This is most likely due to the significantly lower affinity of the Ad7 and Ad14 knobs for CD46, which would require micromolar concentrations of fiber knobs to achieve a measurable blockage of Ad11 binding. Total blockage of Ad11 binding was never observed, probably due to nonspecific binding or binding to secondary or additional receptors (50,53). Ad-blocking experiments usually do not result in complete blocking, as was also observed by others (43,44).…”

Section: Vol 83 2009 a Species B Ad Knob Switch Determines Engagemementioning

confidence: 57%

An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46

Persson

Müller

Reiter

et al. 2009

J Virol

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Adenoviruses (Ads) are icosahedral, nonenveloped viruses with a double-stranded DNA genome. The 51 known Ad serotypes exhibit profound variations in cell tropism and disease types. The number of observed Ad infections is steadily increasing, sometimes leading to fatal outcomes even in healthy individuals. Species B Ads can cause kidney infections, hemorrhagic cystitis, and severe respiratory infections, and most of them use the membrane cofactor protein CD46 as a cellular receptor. The crystal structure of the human Ad type 11 (Ad11) knob complexed with CD46 is known; however, the determinants of CD46 binding in related species B Ads remain unclear. We report here a structural and functional analysis of the Ad11 knob, as well as the Ad7 and Ad14 knobs, which are closely related in sequence to the Ad11 knob but have altered CD46-binding properties. The comparison of the structures of the three knobs, which we determined at very high resolution, provides a platform for understanding these differences and allows us to propose a mechanism for productive high-affinity engagement of CD46. At the center of this mechanism is an Ad knob arginine that needs to switch its orientation in order to engage CD46 with high affinity. Quantum chemical calculations showed that the CD46-binding affinity of Ad11 is significantly higher than that of Ad7. Thus, while Ad7 and Ad14 also bind CD46, the affinity and kinetics of these interactions suggest that these Ads are unlikely to use CD46 productively. The proposed mechanism is likely to determine the receptor usage of all CD46-binding Ads.The nonenveloped adenoviruses (Ads) typically cause respiratory infections, with symptoms ranging from the common cold to pneumonia, but they can also infect the eye, urinary tract, and intestine. Individuals with compromised immune systems are especially prone to severe and life-threatening infections caused by Ads (24). The virion measures about 800 Å in diameter and carries a double-stranded DNA genome. Its icosahedral capsid is primarily formed by 240 copies of the hexon and 12 copies of the penton proteins (3). A trimeric, elongated protein called "fiber" protrudes from each of the 12 vertices of the capsid and mediates the initial attachment to target cells by interacting with cell surface receptors. The fiber consists of a globular head, a fibrous shaft, and a tail. The knob mediates interactions with receptors, whereas the tail anchors the fiber to the penton base. The engagement of receptors is followed by viral internalization via clathrin-coated endocytosis (54).A group of highly pathogenic species B Ads use the membrane cofactor protein CD46 as their cellular receptor (18,20,25,44,50). The heavily glycosylated extracellular portion of CD46 is composed of four short consensus repeat (SCR) modules and a 25-amino-acid sequence rich in serine, threonine, and proline residues (the STP region). CD46 inhibits complement activation by binding separately to C3b or C4b and stabilizes them for proteolytic cleavage by factor I, thus preventing conti...

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Section: Vol 83 2009 a Species B Ad Knob Switch Determines Engagemementioning

confidence: 57%

An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46

Persson

Müller

Reiter

et al. 2009

J Virol

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“…(total liposome projected area)/(cell surface area)], where k f,0 is the association rate in the absence of any steric limitations (36). It is also assumed that liposomes cannot freely access the portion of the cell surface that is adherent to the tissue culture plastic-roughly 50%.…”

Section: Kinetic Computational Modelmentioning

confidence: 99%

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Hendriks

Klinz

Reynolds

et al. 2013

Molecular Cancer Therapeutics

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Numerous targeted nanotherapeutics have been described for potential treatment of solid tumors. Although attention has focused on antigen selection and molecular design of these systems, there has been comparatively little study of how cellular heterogeneity influences interaction of targeted nanoparticles with tumor cells. Antigens, such as HER2/ERBB2, are heterogeneously expressed across different indications, across patients, and within individual tumors. Furthermore, antigen expression in nontarget tissues necessitates optimization of the therapeutic window. Understanding the performance of a given nanoparticle under different regimens of antigen expression has the ability to inform patient selection and clinical development decisions. In this work, HER2-targeted liposomal doxorubicin was used as a modeltargeted nanoparticle to quantitatively investigate the effect of HER2 expression levels on delivery of doxorubicin to the nucleus. We find quantitatively greater nuclear doxorubicin delivery with increasing HER2 expression, exhibiting a threshold effect at approximately 2 Â 10 5 HER2 receptors/cell. Kinetic modeling indicated that the threshold effect arises from multiple low-affinity interactions between the targeted liposome and HER2. These results support previous data showing little or no uptake into human cardiomyocytes, which express levels of HER2 below the threshold. Finally, these results suggest that HER2-targeted liposomal doxorubicin may effectively target tumors that fall below traditional definitions of HER2-positive tumors, thereby expanding the potential population of patients that might benefit from this agent. Mol Cancer Ther; 12(9); 1816-28. Ó2013 AACR.

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“…Therefore, we investi- gated the mode and kinetics of baculovirus entry into mammalian cells. Baculovirus is taken up in insect cells by receptormediated endocytosis, followed by pH-dependent fusion of the envelope with the endosome (3,34). It has been suggested that baculovirus enters mammalian cells by the same pathway because chloroquine strongly inhibits marker gene expression (6,17).…”

Section: Infection Of Mammalian Cells By Baculovirusmentioning

confidence: 99%

“…It has a 130-kb double-stranded DNA genome, packaged in a cigar-shaped (25 by 260 nm) enveloped nucleocapsid. Baculovirus enters insect cells via receptor-mediated endocytosis (32,34). The viral fusion protein gp64 is responsible for acid-induced endosomal escape (3).…”

mentioning

confidence: 99%

Baculovirus Infection of Nondividing Mammalian Cells: Mechanisms of Entry and Nuclear Transport of Capsids

Loo

Fortunati

Ehlert

et al. 2001

J Virol

163

141

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We have studied the infection pathway of Autographa californica multinuclear polyhedrosis virus (baculovirus) in mammalian cells. By titration with a baculovirus containing a green fluorescent protein cassette, we found that several, but not all, mammalian cell types can be infected efficiently. In contrast to previous suggestions, our data show that the asialoglycoprotein receptor is not required for efficient infection. We demonstrate for the first time that this baculovirus can infect nondividing mammalian cells, which implies that the baculovirus is able to transport its genome across the nuclear membrane of mammalian cells. Our data further show that the virus enters via endocytosis, followed by an acid-induced fusion event, which releases the nucleocapsid into the cytoplasm. Cytochalasin D strongly reduces the infection efficiency but not the delivery of nucleocapsids to the cytoplasm, suggesting involvement of actin filaments in cytoplasmic transport of the capsids. Electron microscopic analysis shows the cigar-shaped nucleocapsids located at nuclear pores of nondividing cells. Under these conditions, we observed the viral genome, major capsid protein, and electrondense capsids inside the nucleus. This suggests that the nucleocapsid is transported through the nuclear pore. This mode of transport seems different from viruses with large spherical capsids, such as herpes simplex virus and adenovirus, which are disassembled before nuclear transport of the genome. The implications for the application of baculovirus or its capsid proteins in gene therapy are discussed.The study of host-virus interactions not only contributes to our basic knowledge of virology and cell biology but also is important in the further development of gene therapy vector systems (31). We (35) and others (reviewed in reference 4) have observed that the nuclear transport of vector DNA is a major barrier in the transfection of nondividing cells and hence in the application of nonviral gene therapy vectors in vivo. Several DNA-viruses have found an effective solution to this problem (33). The nucleocapsids of adenovirus (14, 15) and the enveloped herpes simplex virus (HSV) (1, 27) are actively transported toward the nucleus and subsequently dock at the nuclear pore. This triggers the release and nuclear transport of the viral genome. The mechanism of this process and the proteins involved are not known. In both cases a nucleocapsid residue is observed at the nuclear pore. However, it is likely that viral proteins are associated with the DNA during transport (14). Nuclear transport of the viral genome depends on the previous process of entry, which may include a passage through the acidic endosomal environment. During this process the viral capsid is modified to allow the next step in the infection sequence (15,33). This entry-dependent modification of viral capsids allows the important functional distinction between an infecting capsid coming in and a newly formed capsid going out of the cell. Detailed knowledge of the nuclear transport pr...

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General analysis of receptor-mediated viral attachment to cell surfaces

Cited by 101 publications

References 51 publications

An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46

An Arginine Switch in the Species B Adenovirus Knob Determines High-Affinity Engagement of Cellular Receptor CD46

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Baculovirus Infection of Nondividing Mammalian Cells: Mechanisms of Entry and Nuclear Transport of Capsids

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