scholarly journals The Human Adenovirus Type 5 E1B 55 kDa Protein Obstructs Inhibition of Viral Replication by Type I Interferon in Normal Human Cells

2012 ◽  
Vol 8 (8) ◽  
pp. e1002853 ◽  
Author(s):  
Jasdave S. Chahal ◽  
Ji Qi ◽  
S. J. Flint
Keyword(s):  
Viral Replication ◽  
Type I Interferon ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Human Cells ◽  
Type I ◽  
Normal Human ◽  
Normal Human Cells ◽  
Adenovirus Type 5

scholarly journals Type I Interferon-Sensitive Recombinant Newcastle Disease Virus for Oncolytic Virotherapy

2010 ◽  
Vol 84 (8) ◽  
pp. 3835-3844 ◽  
Author(s):  
Subbiah Elankumaran ◽  
Vrushali Chavan ◽  
Dan Qiao ◽  
Raghunath Shobana ◽  
Gopakumar Moorkanat ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Tumor Cells ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Human Cells ◽  
Type I ◽  
V Protein ◽  
Normal Human ◽  
Normal Human Cells ◽  
Tumor Selective

ABSTRACT Newcastle disease virus (NDV), an avian paramyxovirus, is tumor selective and intrinsically oncolytic because of its potent ability to induce apoptosis. Several studies have demonstrated that NDV is selectively cytotoxic to tumor cells but not normal cells due to defects in the interferon (IFN) antiviral responses of tumor cells. Many naturally occurring strains of NDV have an intact IFN-antagonistic function and can still replicate in normal human cells. To avoid potential toxicity issues with NDV, especially in cancer patients with immunosuppression, safe NDV-oncolytic vectors are needed. We compared the cell killing abilities of (i) a recombinant NDV (rNDV) strain, Beaudette C, containing an IFN-antagonistic, wild-type V protein (rBC), (ii) an isogenic recombinant virus with a mutant V protein (rBC-Edit virus) that induces increased IFN in infected cells and whose replication is restricted in normal human cells, and (iii) a recombinant LaSota virus with a virulent F protein cleavage site that is as interferon sensitive as rBC-Edit virus (LaSota V.F. virus). Our results indicated that the tumor-selective replication of rNDV is determined by the differential regulation of IFN-α and downstream antiviral genes induced by IFN-α, especially through the IRF-7 pathway. In a nude mouse model of human fibrosarcoma, we show that the IFN-sensitive NDV variants are as effective as IFN-resistant rBC virus in clearing the tumor burden. In addition, mice treated with rNDV exhibited no signs of toxicity to the viruses. These findings indicate that augmentation of innate immune responses by NDV results in selective oncolysis and offer a novel and safe virotherapy platform.

scholarly journals Effects of Adenovirus Type 5 E1A Isoforms on Viral Replication in Arrested Human Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140124 ◽  
Author(s):  
Sandi Radko ◽  
Richard Jung ◽  
Oladunni Olanubi ◽  
Peter Pelka
Keyword(s):  
Viral Replication ◽  
Adenovirus Type ◽  
Human Cells ◽  
Adenovirus Type 5

Synthesis and in vitro Study of Antiviral and Virucidal Activity of Novel 2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide Derivatives

2011 ◽  
Vol 66 (7-8) ◽  
pp. 333-339
Author(s):  
Monika Wujec ◽  
Tomasz Plech ◽  
Agata Siwek ◽  
Barbara Rajtar ◽  
Małgorzata Polz-Dacewicz
Keyword(s):  
Viral Replication ◽  
Elemental Analysis ◽  
In Vitro Study ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Virucidal Activity ◽  
Hek 293 ◽  
H Nmr ◽  
Adenovirus Type 5

2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide derivatives were synthesized and their structures were confirmed by 1H NMR, IR, and elemental analysis. Cytotoxicity of the compounds towards HEK-293 and GMK cells was evaluated. Moreover, the antiviral and virucidal activities of these compounds against human adenovirus type 5 and ECHO-9 virus were assessed. Some of the newly synthesized derivatives have the potential to reduce the viral replication of both tested viruses.

scholarly journals Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

2009 ◽  
Vol 381 (2) ◽  
pp. 288-293 ◽  
Author(s):  
Laura W. McMahon ◽  
Pan Zhang ◽  
Deepa M. Sridharan ◽  
Joel A. Lefferts ◽  
Muriel W. Lambert
Keyword(s):  
Chromosomal Instability ◽  
Human Cells ◽  
Cross Link ◽  
Normal Human ◽  
Normal Human Cells

scholarly journals In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1483
Author(s):  
Emily A. Bates ◽  
John R. Counsell ◽  
Sophie Alizert ◽  
Alexander T. Baker ◽  
Natalie Suff ◽  
...  
Keyword(s):  
Viral Vector ◽  
Ex Vivo ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Cell Types ◽  
In Vivo Evaluation ◽  
In Vivo Biodistribution ◽  
Adenovirus Type 5

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications.

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