bacteriophage t4
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Author(s):  
Jingen Zhu ◽  
Neeti Ananthaswamy ◽  
Swati Jain ◽  
Himanshu Batra ◽  
Wei-Chun Tang ◽  
...  

Author(s):  
Xinjie Chen ◽  
Yuan Lu

Circular RNA (circRNA) is a unique type of noncoding RNA molecule. Compared with traditional linear RNA, circRNA is a covalently closed circle produced by a process called backsplicing. CircRNA is abundant in many cells and has rich functions in cells, such as acting as miRNA sponge, protein sponge, protein scaffold, and mRNA regulator. With the continuous development of circRNA study, circRNA has also played an important role in medical applications, including circRNA vaccines and gene therapy. In this review, we illustrate the synthesis of circRNAs in vitro. We focus on biological ligation methods, such as enzymatic ligation from the bacteriophage T4 and ribozyme method. In addition, we summarize the current challenges in the design, synthesis, application, and production of circRNAs, and propose possible solutions in the future. CircRNA is expected to play an essential role in basic research and medical applications.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Li Dai ◽  
Digvijay Singh ◽  
Suoang Lu ◽  
Vishal I. Kottadiel ◽  
Reza Vafabakhsh ◽  
...  

AbstractMulti-subunit ring-ATPases carry out a myriad of biological functions, including genome packaging in viruses. Though the basic structures and functions of these motors have been well-established, the mechanisms of ATPase firing and motor coordination are poorly understood. Here, using single-molecule fluorescence, we determine that the active bacteriophage T4 DNA packaging motor consists of five subunits of gp17. By systematically doping motors with an ATPase-defective subunit and selecting single motors containing a precise number of active or inactive subunits, we find that the packaging motor can tolerate an inactive subunit. However, motors containing one or more inactive subunits exhibit fewer DNA engagements, a higher failure rate in encapsidation, reduced packaging velocity, and increased pausing. These findings suggest a DNA packaging model in which the motor, by re-adjusting its grip on DNA, can skip an inactive subunit and resume DNA translocation, suggesting that strict coordination amongst motor subunits of packaging motors is not crucial for function.


Author(s):  
Rupy Kaur Matharu ◽  
Yuen-Ki Cheong ◽  
Guogang Ren ◽  
Mohan Edirisinghe ◽  
Lena Ciric

Abstract Viral pandemic outbreaks cause a significant burden on global health as well as healthcare expenditure. The use of antiviral agents not only reduces the spread of viral pathogens but also diminishes the likelihood of them causing infection. The antiviral properties of novel copper-silver and copper-zinc intermetallic nanoparticles against Escherichia coli bacteriophage MS2 (RNA virus) and Escherichia coli bacteriophage T4 (DNA virus) are presented. The intermetallic nanoparticles were spherical in shape and were between 90 and 120 nm. Antiviral activity was assessed at concentrations ranging from 0.05 to 2.0 wt/v% for 3 and 24 h using DNA and RNA virus model organisms. Both types of nanoparticles demonstrated strong potency towards RNA viruses (> 89% viral reduction), whilst copper-silver nanoparticles were slightly more toxic towards DNA viruses when compared to copper-zinc nanoparticles. Both nanoparticles were then incorporated into polymeric fibres (carrier) to investigate their antiviral effectiveness when composited into polymeric matrices. Fibres containing copper-silver nanoparticles exhibited favourable antiviral properties, with a viral reduction of 75% after 3 h of exposure. The excellent antiviral properties of the intermetallic nanoparticles reported in this study against both types of viruses together with their unique material properties can make them significant alternatives to conventional antiviral therapies and decontamination agents.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengling Li ◽  
Pengju Guo ◽  
Cen Chen ◽  
Helong Feng ◽  
Wanpo Zhang ◽  
...  

Developing influenza vaccines that protect against a broad range of viruses is a global health priority. Several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is sufficiently immunogenic to elicit complete protection, and vaccine platforms that can enhance immunogenicity and deliver multiple antigens are desperately needed. Here, we report proof-of-concept studies for the development of next-generation influenza vaccines using the bacteriophage T4 virus-like particle (VLP) platform. Using the extracellular domain of influenza matrix protein 2 (M2e) as a readout, we demonstrate that up to ~1,281 M2e molecules can be assembled on a 120 x 86 nanometer phage capsid to generate M2e-T4 VLPs. These M2e-decorated nanoparticles, without any adjuvant, are highly immunogenic, stimulate robust humoral as well as cellular immune responses, and conferred complete protection against lethal influenza virus challenge. Potentially, additional conserved antigens could be incorporated into the M2e-T4 VLPs and mass-produced in E. coli in a short amount of time to deal with an emerging influenza pandemic.


2021 ◽  
Vol 7 (37) ◽  
Author(s):  
Jingen Zhu ◽  
Neeti Ananthaswamy ◽  
Swati Jain ◽  
Himanshu Batra ◽  
Wei-Chun Tang ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1739
Author(s):  
Chen-Yu Lo ◽  
Yang Gao

Bacteriophages have long been model systems to study the molecular mechanisms of DNA replication. During DNA replication, a DNA helicase and a DNA polymerase cooperatively unwind the parental DNA. By surveying recent data from three bacteriophage replication systems, we summarized the mechanistic basis of DNA replication by helicases and polymerases. Kinetic data have suggested that a polymerase or a helicase alone is a passive motor that is sensitive to the base-pairing energy of the DNA. When coupled together, the helicase–polymerase complex is able to unwind DNA actively. In bacteriophage T7, helicase and polymerase reside right at the replication fork where the parental DNA is separated into two daughter strands. The two motors pull the two daughter strands to opposite directions, while the polymerase provides a separation pin to split the fork. Although independently evolved and containing different replisome components, bacteriophage T4 replisome shares mechanistic features of Hel–Pol coupling that are similar to T7. Interestingly, in bacteriophages with a limited size of genome like Φ29, DNA polymerase itself can form a tunnel-like structure, which encircles the DNA template strand and facilitates strand displacement synthesis in the absence of a helicase. Studies on bacteriophage replication provide implications for the more complicated replication systems in bacteria, archaeal, and eukaryotic systems, as well as the RNA genome replication in RNA viruses.


Author(s):  
Douglas E. Smith ◽  
Youbin E. Mo ◽  
Nick Keller ◽  
Damian delToro ◽  
Neeti Ananthaswamy ◽  
...  

2021 ◽  
Author(s):  
Himanshu Batra ◽  
Jingen Zhu ◽  
Swati Jain ◽  
Neeti Ananthaswamy ◽  
Marthandan Mahalingam ◽  
...  

The latent HIV-1 reservoir containing stably integrated and transcriptionally silent proviruses in CD4+ T cells is a major barrier for virus eradication. Targeted reactivation of the latent reservoir remains a major challenge in establishing a path for an HIV-1 cure. Here, we investigated the possibility of reactivating the HIV-1 reservoir by targeting engineered bacteriophage T4 capsid nanoparticles to reservoir cells. The surface lattice of the 120 x 86 nm phage capsid was arrayed with CD4 binding ligands such as recombinant CD4DARPin or the HIV-1 gp140 envelope protein. When exposed to either PBMCs or the resting CD4+ T cells in vitro, these nanoparticles caused T cells activation without inducing global T cell activation. Furthermore, the nanoparticles reactivated HIV-1 proviral transcription that led to virus assembly and release in the J-Lat cells, a cell line model of HIV-1 latency. Intriguingly, the observed T cell activation and HIV-1 latency reversal did not occur through the classic PKC or NFAT pathways suggesting the involvement of a yet unknown pathway. These studies demonstrate that engineered non-infectious bacteriophages could be potentially exploited for HIV-1 cure and other targeted T cell therapies.


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