Virology
Vectors for Cancer Therapy
Oncolytic HSV (oHSV) virotherapy is a promising new strategy for cancer therapy, converting a human pathogen into a therapeutic agent. This takes advantage of the biology of HSV, by introducing genetic alterations that limit virus replication and cytotoxicity to transformed cancer cells while making the virus non-permissive in normal cells. HSV encodes a large number of genes that are non-essential for growth in tissue culture cells, but are nevertheless important for growth in post-mitotic cells and for interfering with intrinsic antiviral and innate immune responses. Many of the cellular pathways regulating growth and antiviral responses are disrupted in cancer cells, which means that viral gene products allowing replication in normal cells are not necessary in cancer cells. In considering the development of an infectious agent for human use, safety is a critical consideration. Therefore mutations targeting cancer cells must be combined with mutations in genes that play important roles in vivo; causing pathogenicity, spread through the nervous system and other organs, latency and reactivation, and adaptive immune responses. This review will focus more on the virological aspects of oHSV vectors and less on the cancer cell target, and describe the multiple strategies and genes involved in generating oHSV vectors. However, it is important to bear in mind that the effect of different HSV mutations will be highly dependent upon the physiology of the particular type of cancer cell and tumor, and that each oHSV vector will be more effective in some tumor types, so that it is unlikely that any one oHSV will be optimal for all types of cancer.
Further reading: Alphaherpesviruses: Molecular Virology
Further reading: Alphaherpesviruses: Molecular Virology
Autophagy
Autophagy is a rapidly growing area of biomedical research with broad relevance to fields including microbiology, cell biology, immunology, cancer biology, and neurodegeneration. In infection and immunity, it is emerging as a pivotal pathway mediating direct pathogen degradation as well as for the development of robust innate and adaptive immune responses. Successful pathogens have evolved to either evade or harness the autophagy pathway to further their replication and pathogenesis. In a recent review the basic aspects of autophagy will be described, along with its role in cellular homeostasis, and the development of immunity. The primary focus is a survey of past and recent research defining the interplay of autophagy and the herpesviruses, with particular reference to immune evasion and pathogenesis.
Further reading: Alphaherpesviruses: Molecular Virology
Further reading: Alphaherpesviruses: Molecular Virology
Human Alpha-herpesvirus MicroRNAs
MicroRNAs (miRNAs) are an extensive class of approx 22 nucleotide long regulatory RNAs expressed by all mammalian cells and also by several DNA viruses, including many members of the herpesvirus family. Using deep sequencing technology, it has now been demonstrated that Herpes Simplex Virus 1 (HSV-1) encodes at least eight viral miRNAs, seven of which are expressed in latently infected human neurons. Similarly, HSV-2 has also been shown to encode at least six miRNAs, four of which are evolutionarily conserved between HSV-2 and HSV-1. Perhaps surprisingly, varicella zoster virus does not appear to express any viral miRNAs in latently infected cells. A recent review discusses the potential functions of the currently known HSV-1 and HSV-2 miRNAs, focusing on a possible role in stabilizing viral latency in infected neurons.
Further reading: Alphaherpesviruses: Molecular Virology
Further reading: Alphaherpesviruses: Molecular Virology
Plant Viral Vectors for Protein Expression
Plant Viral Vectors for Protein Expression
from Yuri Y. Gleba and Anatoli Giritch writing in Recent Advances in Plant Virology
Plant-virus-driven transient expression of heterologous proteins is the basis of several mature manufacturing processes that are currently being used for the production of multiple proteins including vaccine antigens and antibodies. Viral vectors have also become useful tools for research. In recent years, advances have been made both in the development of first-generation vectors (those that employ the 'full virus' strategy) as well as second-generation vectors designed using the 'deconstructed virus' approach. This second strategy relies on Agrobacterium as a vector to deliver DNA copies of one or more viral RNA replicons. Among the most often used viral backbones are those of Tobacco mosaic virus, Potato virus X, and Cowpea mosaic virus. Prototypes of industrial processes that provide for high-yield, rapid scale-up, and fast manufacturing have been recently developed using viral vectors, with several manufacturing facilities compliant with good manufacturing practices (GMP) in place, and a number of pharmaceutical proteins currently in pre-clinical and clinical trials.
Further reading: Recent Advances in Plant Virology | Virology Publications
from Yuri Y. Gleba and Anatoli Giritch writing in Recent Advances in Plant Virology
Plant-virus-driven transient expression of heterologous proteins is the basis of several mature manufacturing processes that are currently being used for the production of multiple proteins including vaccine antigens and antibodies. Viral vectors have also become useful tools for research. In recent years, advances have been made both in the development of first-generation vectors (those that employ the 'full virus' strategy) as well as second-generation vectors designed using the 'deconstructed virus' approach. This second strategy relies on Agrobacterium as a vector to deliver DNA copies of one or more viral RNA replicons. Among the most often used viral backbones are those of Tobacco mosaic virus, Potato virus X, and Cowpea mosaic virus. Prototypes of industrial processes that provide for high-yield, rapid scale-up, and fast manufacturing have been recently developed using viral vectors, with several manufacturing facilities compliant with good manufacturing practices (GMP) in place, and a number of pharmaceutical proteins currently in pre-clinical and clinical trials.
Further reading: Recent Advances in Plant Virology | Virology Publications
Book Review: RNAi and Viruses
"The use of RNA interference to control gene expression is emerging as an exciting new technology. The potential of this mechanism depends on the ability to find a competent way to deliver the RNA. This compact book reviews all of these issues in a comprehensive manner." from Doodys (2010)
Further reading: RNA Interference and Viruses: Current Innovations and Future Trends
Further reading: RNA Interference and Viruses: Current Innovations and Future Trends