scholarly journals Activation of innate immune responses by a CpG oligonucleotide sequence composed entirely of threose nucleic acid

2018 ◽  
Author(s):  
Margaret J. Lange ◽  
Donald H. Burke ◽  
John C. Chaput

AbstractRecent advances in synthetic biology have led to the development of nucleic acid polymers with backbone structures distinct from those found in nature, termed xeno-nucleic acids (XNAs). Several unique properties of XNAs make them attractive as nucleic acid therapeutics, most notably their high resistance to serum nucleases and ability to form Watson-Crick base-pairing with DNA and RNA. The ability of XNAs to induce immune responses has not been investigated. Threose nucleic acid (TNA), a type of XNA, is recalcitrant to nuclease digestion and capable of undergoing Darwinian evolution to produce high affinity aptamers; thus, TNA is an attractive candidate for diverse applications, including nucleic acid therapeutics. Here, we evaluated a TNA oligonucleotide derived from a CpG oligonucleotide sequence known to activate TLR9-dependent immune signaling in B cell lines. We observed a slight induction of relevant mRNA signals, robust B cell line activation, and negligible effects on cellular proliferation.




Author(s):  
Bryan C. Mounce ◽  
Michelle E. Olsen ◽  
Marco Vignuzzi ◽  
John H. Connor

SUMMARY Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic acid conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis. Understanding the role of polyamines has become easier with the application of small-molecule inhibitors of polyamine synthesis and the use of interferon-induced regulators of polyamines. Here we review the diverse mechanisms in which viruses require polyamines and investigate blocking polyamine synthesis as a potential broad-spectrum antiviral approach.



2020 ◽  
Author(s):  
Shahan Mamoor

While adaptive immune responses involve antigen-specific responses, rapid innate immune responses involve detection of pathogen-associated molecular patterns such as the nucleic acids DNA and RNA (1). We mined five independent microarray datasets (2-6) to discover in an unbiased and systematic fashion pattern recognition receptors associated with coronavirus infection across a series of coronaviruses capable of infecting humans. We describe here the transcriptional induction of four nucleic acid and PAMP sensors following coronavirus infection in vitro and in vivo: Z-DNA-binding protein ZBP1, the DExH-box helicase DHX58 (LGP2), PYHIN1 and the Mediterannean Fever gene PYRIN as among the genes most differentially expressed following infection with coronaviruses. These data reveal unprecedented mobilization of nucleic acid sensors during coronavirus infection.



Author(s):  
B.A. Hamkalo ◽  
S. Narayanswami ◽  
A.P. Kausch

The availability of nonradioactive methods to label nucleic acids an the resultant rapid and greater sensitivity of detection has catapulted the technique of in situ hybridization to become the method of choice to locate of specific DNA and RNA sequences on chromosomes and in whole cells in cytological preparations in many areas of biology. It is being applied to problems of fundamental interest to basic cell and molecular biologists such as the organization of the interphase nucleus in the context of putative functional domains; it is making major contributions to genome mapping efforts; and it is being applied to the analysis of clinical specimens. Although fluorescence detection of nucleic acid hybrids is routinely used, certain questions require greater resolution. For example, very closely linked sequences may not be separable using fluorescence; the precise location of sequences with respect to chromosome structures may be below the resolution of light microscopy(LM); and the relative positions of sequences on very small chromosomes may not be feasible.



2019 ◽  
Vol 19 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Marzieh Rezaei ◽  
Mohammad Rabbani-khorasgani ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Rahman Emamzadeh ◽  
Hamid Abtahi

Background:Brucellosis is an infectious disease caused by Brucella bacteria that cause disease in animals and humans. Brucellosis is one of the most common zoonotic diseases transmitted from animals-to-human through direct contact with infected animals and also consumption of unpasteurized dairy products. Due to the wide incidence of brucellosis in Iran and economical costs in industrial animal husbandry, Vaccination is the best way to prevent this disease. All of the available commercial vaccines against brucellosis are derived from live attenuated strains of Brucella but because of the disadvantage of live attenuated vaccines, protective subunit vaccine against Brucella may be a good candidate for the production of new recombinant vaccines based on Brucella Outer Membrane Protein (OMP) antigens. In the present study, comprehensive bioinformatics analysis has been conducted on prediction software to predict T and B cell epitopes, the secondary and tertiary structures and antigenicity of Omp16 antigen and the validation of used software confirmed by experimental results.Conclusion:The final epitope prediction results have proposed that the three epitopes were predicted for the Omp16 protein with antigenicity ability. We hypothesized that these epitopes likely have the protective capacity to stimulate both the B-cell and T-cell mediated immune responses and so may be effective as an immunogenic candidate for the development of an epitope-based vaccine against brucellosis.



2021 ◽  
Author(s):  
Ya Ying Zheng ◽  
Ying Wu ◽  
Thomas Begley ◽  
Jia Sheng

Sulfur modifications have been discovered on both DNA and RNA. Sulfur substitution of oxygen atoms at nucleobase or backbone locations in the nucleic acid framework led to a wide variety...



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