Structure of a cell entry defective human adenovirus provides insights into precursor proteins and capsid maturation

2021 ◽  
pp. 167350
Author(s):  
Xiaodi Yu ◽  
Tina-Marie Mullen ◽  
Vahid Abrishami ◽  
Juha T. Huiskonen ◽  
Glen R. Nemerow ◽  
...  
Keyword(s):  
Human Adenovirus ◽  
Cell Entry ◽  
Precursor Proteins ◽  
A Cell ◽  
Capsid Maturation

scholarly journals Cell Entry and Trafficking of Human Adenovirus Bound to Blood Factor X Is Determined by the Fiber Serotype and Not Hexon:Heparan Sulfate Interaction

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e18205 ◽  
Author(s):  
Stéphanie Corjon ◽  
Gaëlle Gonzalez ◽  
Petra Henning ◽  
Alexei Grichine ◽  
Leif Lindholm ◽  
...  
Keyword(s):  
Human Adenovirus ◽  
Cell Entry ◽  
Factor X

scholarly journals Processing of GB virus B non-structural proteins in cultured cells requires both NS3 protease and NS4A cofactor

2000 ◽  
Vol 81 (9) ◽  
pp. 2183-2188 ◽  
Author(s):  
Andrea Sbardellati ◽  
Elisa Scarselli ◽  
Viviana Amati ◽  
Sabrina Falcinelli ◽  
Alexander S. Kekulé ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Structural Model ◽  
Cultured Cells ◽  
Structural Proteins ◽  
Cleavage Sites ◽  
Mature Protein ◽  
Precursor Proteins ◽  
A Cell ◽  
Ns3 Protease

The identification of antivirals and vaccines against hepatitis C virus (HCV) infection is hampered by the lack of convenient animal models. The need to develop surrogate models has recently drawn attention to GB virus B (GBV-B), which produces hepatitis in small primates. In a previous study in vitro, it was shown that GBV-B NS3 protease shares substrate specificity with the HCV enzyme, known to be crucial for virus replication. In this report, GBV-B NS3 activity on GBV-B precursor proteins has been analysed in a cell-based system. It is shown that mature protein products are obtained that are compatible with the cleavage sites proposed on the basis of sequence homology with HCV and that GBV-B NS4A protein is required as a cofactor for optimal enzymatic activity. Experiments in vitro supported by a structural model mapped the region of NS4A that interacts with NS3 and showed that the GBV-B cofactor cannot be substituted for by its HCV analogue.

scholarly journals Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46

2020 ◽  
Vol 118 (3) ◽  
pp. e2020732118
Author(s):  
B. David Persson ◽  
Lijo John ◽  
Karim Rafie ◽  
Michael Strebl ◽  
Lars Frängsmyr ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Direct Interaction ◽  
Human Adenovirus ◽  
Host Cells ◽  
Screening Assay ◽  
Vaccine Vectors ◽  
Fiber Protein ◽  
A Cell ◽  
Microscopy Analysis ◽  
Infection Experiments

Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion–CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors.

scholarly journals Activation of a Cell Entry Pathway Common to Type C Mammalian Retroviruses by Soluble Envelope Fragments

2000 ◽  
Vol 74 (1) ◽  
pp. 295-304 ◽  
Author(s):  
Dimitri Lavillette ◽  
Alessia Ruggieri ◽  
Stephen J. Russell ◽  
François-Loïc Cosset
Keyword(s):  
Specific Interaction ◽  
Cell Entry ◽  
Target Cells ◽  
Amino Terminal ◽  
Entry Pathway ◽  
Defective Mutant ◽  
Fusion Defect ◽  
A Cell ◽  
Type C ◽  
Leukemia Viruses

ABSTRACT Mutations that negatively or positively affect the fusion properties of murine leukemia viruses (MLVs) have been found within all subdomains of their SU (surface) and TM (transmembrane) envelope units. Yet, the interrelations between these different regions of the envelope complex during the cell entry process are still elusive. Deletion of the histidine residue of the conserved PHQV motif at the amino terminus of the amphotropic or the ecotropic MLV SU resulted in the AdelH or the MOdelH fusion-defective mutant envelope, respectively. These delH mutant envelopes are incorporated on retroviral particles at normal densities and normally mediate virion binding to cells expressing the retroviral receptors. However, both their cell-cell and virus-cell fusogenicities were fully prevented at an early postbinding stage. We show here that the fusion defect of AdelH or MOdelH envelopes was also almost completely reverted by providing either soluble SU or a polypeptide encompassing the receptor-binding domain (RBD) to the target cells, provided that the integrity of the amino-terminal end of either polypeptide was preserved. Restoration of delH envelope fusogenicity was caused by activation of the target cells via specific interaction of the latter polypeptides with the retrovirus receptor rather than by their association with the delH envelope complexes. Moreover crossactivation of the target cells, leading to fusion activation of AdelH or MOdelH envelopes, was achieved by polypeptides containing various type C mammalian retrovirus RBDs, irrespective of the type of entry-defective glycoprotein that was used for infection. Our results indicate that although they recognize different receptors for binding to the cell surface, type C mammalian retroviruses use a common entry pathway which is activated by a conserved feature of their envelope glycoproteins.

scholarly journals Ganglioside GD1a Restores Infectibility to Mouse Cells Lacking Functional Receptors for Polyomavirus

2005 ◽  
Vol 79 (1) ◽  
pp. 615-618 ◽  
Author(s):  
Joanna Gilbert ◽  
Jean Dahl ◽  
Cathy Riney ◽  
John You ◽  
Cunqi Cui ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
Simian Virus ◽  
Cell Entry ◽  
Heterologous Host ◽  
Virus Binding ◽  
Rat Glioma ◽  
Caveolin 1 ◽  
Ganglioside Biosynthesis ◽  
A Cell ◽  
Mouse Cells

ABSTRACT Recent investigations on the pathway of cell entry by polyomavirus (Py) and simian virus 40 (SV40) have defined specific gangliosides as functional receptors mediating virus binding and transport from the plasma membrane to the endoplasmic reticulum (B. Tsai et al., EMBO J. 22:4346-4355, 2003; Gilbert and Benjamin, in press). These studies were carried out with C6 rat glioma cells, a heterologous host chosen for its known deficiency in ganglioside biosynthesis. Here, a cell genetic approach was undertaken to identify components required for the early steps of infection using mouse cells as the natural host for Py. Receptor-negative (R−) mouse cells, screened based on resistance to Py infection, were shown to bind Py but failed to allow entry of the virus. R− cells were also found to be resistant to SV40. Infectibility was restored or enhanced by the addition of the same specific gangliosides found in earlier studies with C6 cells. In one R− line, overexpression of caveolin-1 also increased infectibility. These results support and extend findings on gangliosides in lipid rafts as functional receptors and mediators of internalization for Py and SV40.

scholarly journals Replication-Deficient Human Adenovirus Type 35 Vectors for Gene Transfer and Vaccination: Efficient Human Cell Infection and Bypass of Preexisting Adenovirus Immunity

2003 ◽  
Vol 77 (15) ◽  
pp. 8263-8271 ◽  
Author(s):  
Ronald Vogels ◽  
David Zuijdgeest ◽  
Richard van Rijnsoever ◽  
Eric Hartkoorn ◽  
Irma Damen ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Cell Infection ◽  
Vector Plasmid ◽  
Gene Therapy Vector ◽  
Immunological Responses ◽  
A Cell ◽  
Minimal Sequence ◽  
Adenovirus Type 5

ABSTRACT Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the identification of human Ad35 as a virus with low global prevalence and the generation of an Ad35 vector plasmid system for easy insertion of heterologous genes. In addition, we have identified the minimal sequence of the Ad35-E1B region (molecular weight, 55,000 [55K]), pivotal for complementation of fully E1-lacking Ad35 vector on PER.C6 cells. After stable insertion of the 55K sequence into PER.C6 cells a cell line was obtained (PER.C6/55K) that efficiently transcomplements both Ad5 and Ad35 vectors. We further demonstrate that transduction with Ad35 is not hampered by preexisting Ad5 immunity and that Ad35 efficiently infects dendritic cells, smooth muscle cells, and synoviocytes, in contrast to Ad5.

Colicins exploit native disorder to gain cell entry: a hitchhiker's guide to translocation

2008 ◽  
Vol 36 (6) ◽  
pp. 1409-1413 ◽  
Author(s):  
Daniel A. Bonsor ◽  
Nicola A. Meenan ◽  
Colin Kleanthous
Keyword(s):  
Protein Interactions ◽  
Nuclease Activity ◽  
Supramolecular Complex ◽  
Membrane Receptors ◽  
Cell Entry ◽  
Periplasmic Protein ◽  
Protein Protein Interactions ◽  
Protein Toxins ◽  
A Cell ◽  
Colicin E9

The translocation of protein toxins into a cell relies on a myriad of protein–protein interactions. One such group of toxins are enzymatic E colicins, protein antibiotics produced by Escherichia coli in times of stress. These proteins subvert ordinary nutrient uptake mechanisms to enter the cell and unleash nuclease activity. We, and others, have previously shown that uptake of ColE9 (colicin E9) is dependent on engagement of the OM (outer membrane) receptors BtuB and OmpF as well as recruitment of the periplasmic protein TolB, forming a large supramolecular complex. Intriguingly, colicins bind TolB using a natively disordered region to mimic the interaction of TolB with Pal (peptidoglycan-associated lipoprotein). This is thought to trigger OM instability and prime the system for translocation. Here, we review key interactions in the assembly of this ‘colicin translocon’ and discuss the key role disorder plays in achieving uptake.

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