scholarly journals Application of CRISPR/Cas9 in Understanding Avian Viruses and Developing Poultry Vaccines

Author(s):  
Julianne Vilela ◽  
Mohammed A. Rohaim ◽  
Muhammad Munir

Clustered regularly interspaced short palindromic repeats associated protein nuclease 9 (CRISPR-Cas9) technology offers novel approaches to precisely, cost-effectively, and user-friendly edit genomes for a wide array of applications and across multiple disciplines. This methodology can be leveraged to underpin host-virus interactions, elucidate viral gene functions, and to develop recombinant vaccines. The successful utilization of CRISPR/Cas9 in editing viral genomes has paved the way of developing novel and multiplex viral vectored poultry vaccines. Furthermore, CRISPR/Cas9 can be exploited to rectify major limitations of conventional approaches including reversion to virulent form, recombination with field viruses and transgene, and genome instability. This review provides comprehensive analysis of the potential of CRISPR/Cas9 genome editing technique in understanding avian virus-host interactions and developing novel poultry vaccines. Finally, we discuss the simplest and practical aspects of genome editing approaches in generating multivalent recombinant poultry vaccines that conform simultaneous protection against major avian diseases.

2020 ◽  
Vol 14 (10) ◽  
pp. 2527-2541 ◽  
Author(s):  
Jessica K. Jarett ◽  
Mária Džunková ◽  
Frederik Schulz ◽  
Simon Roux ◽  
David Paez-Espino ◽  
...  

Abstract Our current knowledge of host–virus interactions in biofilms is limited to computational predictions based on laboratory experiments with a small number of cultured bacteria. However, natural biofilms are diverse and chiefly composed of uncultured bacteria and archaea with no viral infection patterns and lifestyle predictions described to date. Herein, we predict the first DNA sequence-based host–virus interactions in a natural biofilm. Using single-cell genomics and metagenomics applied to a hot spring mat of the Cone Pool in Mono County, California, we provide insights into virus–host range, lifestyle and distribution across different mat layers. Thirty-four out of 130 single cells contained at least one viral contig (26%), which, together with the metagenome-assembled genomes, resulted in detection of 59 viruses linked to 34 host species. Analysis of single-cell amplification kinetics revealed a lack of active viral replication on the single-cell level. These findings were further supported by mapping metagenomic reads from different mat layers to the obtained host–virus pairs, which indicated a low copy number of viral genomes compared to their hosts. Lastly, the metagenomic data revealed high layer specificity of viruses, suggesting limited diffusion to other mat layers. Taken together, these observations indicate that in low mobility environments with high microbial abundance, lysogeny is the predominant viral lifestyle, in line with the previously proposed “Piggyback-the-Winner” theory.


2019 ◽  
Vol 12 (4) ◽  
pp. 147 ◽  
Author(s):  
Sonja C. J. H. Chua ◽  
Hui Qing Tan ◽  
David Engelberg ◽  
Lina H. K. Lim

Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind. Currently available drugs and vaccines only partially reduce deaths and hospitalizations. Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host–pathogen interactions. Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed. These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines. Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches. The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures. In this review, we summarized the efforts to study influenza in yeast, Drosophila, zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease. We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus–host interactions and viral protein function.


2019 ◽  
Vol 5 (2) ◽  
Author(s):  
Gabriel I Parra

Abstract Noroviruses are a very diverse group of viruses that infect different mammalian species. In humans, norovirus is a major cause of acute gastroenteritis. Multiple norovirus infections can occur in a lifetime as the result of limited duration of acquired immunity and cross-protection among different strains. A combination of advances in sequencing methods and improvements on surveillance has provided new insights into norovirus diversification and emergence. The generation of diverse norovirus strains has been associated with (1) point mutations on two different genes: ORF1, encoding the non-structural proteins, and ORF2, encoding the major capsid protein (VP1); and (2) recombination events that create chimeric viruses. While both mechanisms are exploited by all norovirus strains, individual genotypes utilize each mechanism differently to emerge and persist in the human population. GII.4 noroviruses (the most prevalent genotype in humans) present an accumulation of amino acid mutations on VP1 resulting in the chronological emergence of new variants. In contrast, non-GII.4 noroviruses present co-circulation of different variants over long periods with limited changes on their VP1. Notably, genetic diversity of non-GII.4 noroviruses is mostly related to the high number of recombinant strains detected in humans. While it is difficult to determine the precise mechanism of emergence of epidemic noroviruses, observations point to multiple factors that include host-virus interactions and changes on two regions of the genome (ORF1 and ORF2). Larger datasets of viral genomes are needed to facilitate comparison of epidemic strains and those circulating at low levels in the population. This will provide a better understanding of the mechanism of norovirus emergence and persistence.


Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 444 ◽  
Author(s):  
Donna Collins-McMillen ◽  
Jason Buehler ◽  
Megan Peppenelli ◽  
Felicia Goodrum

Human cytomegalovirus (HCMV) is a beta herpesvirus that establishes a life-long persistence in the host, like all herpesviruses, by way of a latent infection. During latency, viral genomes are maintained in a quieted state. Virus replication can be reactivated from latency in response to changes in cellular signaling caused by stress or differentiation. The past decade has brought great insights into the molecular basis of HCMV latency. Here, we review the complex persistence of HCMV with consideration of latent reservoirs, viral determinants and their host interactions, and host signaling and the control of cellular and viral gene expression that contributes to the establishment of and reactivation from latency.


2020 ◽  
Vol 45 (3) ◽  
pp. 241-248
Author(s):  
Engin Yilmaz ◽  
Yakut Akyön ◽  
Muhittin Serdar

AbstractCOVID-19 is the third spread of animal coronavirus over the past two decades, resulting in a major epidemic in humans after SARS and MERS. COVID-19 is responsible of the biggest biological earthquake in the world. In the global fight against COVID-19 some serious mistakes have been done like, the countries’ misguided attempts to protect their economies, lack of international co-operation. These mistakes that the people had done in previous deadly outbreaks. The result has been a greater economic devastation and the collapse of national and international trust for all. In this constantly changing environment, if we have a better understanding of the host-virus interactions than we can be more prepared to the future deadly outbreaks. When encountered with a disease which the causative is unknown, the reaction time and the precautions that should be taken matters a great deal. In this review we aimed to reveal the molecular footprints of COVID-19 scientifically and to get an understanding of the pandemia. This review might be a highlight to the possible outbreaks.


Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Chathura D. Suraweera ◽  
Mark G. Hinds ◽  
Marc Kvansakul

Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause for many diseases. Intrinsic apoptosis is regulated by members of the evolutionarily conserved B-cell lymphoma-2 (Bcl-2) family, a family that consists of pro- and anti-apoptotic members. Bcl-2 genes have also been assimilated by numerous viruses including pox viruses, in particular the sub-family of chordopoxviridae, a group of viruses known to infect almost all vertebrates. The viral Bcl-2 proteins are virulence factors and aid the evasion of host immune defenses by mimicking the activity of their cellular counterparts. Viral Bcl-2 genes have proved essential for the survival of virus infected cells and structural studies have shown that though they often share very little sequence identity with their cellular counterparts, they have near-identical 3D structures. However, their mechanisms of action are varied. In this review, we examine the structural biology, molecular interactions, and detailed mechanism of action of poxvirus encoded apoptosis inhibitors and how they impact on host–virus interactions to ultimately enable successful infection and propagation of viral infections.


Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 232
Author(s):  
Srikanth Elesela ◽  
Nicholas W. Lukacs

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.


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