Human Alpha-herpesvirus MicroRNAs

from Jennifer L. Umbach and Bryan R. Cullen writing in Alphaherpesviruses: Molecular Virology:

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

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

RNA Silencing in Plants

RNA Silencing in Plants and the Role of Viral Suppressors
from Ana Giner, Juan Jose Lopez-Moya and Lorant Lakatos writing in RNA Interference and Viruses
The term RNA silencing refers to several pathways present in eukaryotic organisms that lead to the sequence specific elimination or functional blocking of RNAs with homology to double stranded RNAs (dsRNAs) that have previously triggered the mechanism. Besides playing important roles in developmental control, RNA silencing forms part of the defence against viruses in plants, acting as a potent antiviral mechanism. To escape from the RNA silencing-based defence, most plant viruses make use of different strategies, the most common relying in the action of viral proteins with the capacity to suppress RNA silencing. The characterization of these viral suppressors is providing useful insights to understand how RNA silencing works, revealing components and steps in the silencing pathways.

Further reading: Recent Advances in Plant Virology | RNA Interference and Viruses | RNA and the Regulation of Gene Expression

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

RNA Silencing

RNA Silencing and the Interplay Between Plants and Viruses
from Lourdes Fernández-Calvino, Livia Donaire and César Llave writing in Recent Advances in Plant Virology

In eukaryotes, RNA silencing controls gene expression to regulate development, genome stability and stress-induced responses. In plants, this process is also recognized as a major immune system targeted against plant viruses. Plant viruses stimulate RNA silencing responses though formation of viral RNA with double-stranded features that are subsequently processed into functional small RNAs (sRNAs). Recent studies highlight the complexity of the viral sRNA populations and their potential to associate with multiple silencing effector complexes. This fact has profound implications in the cross-talk interactions between plants and viruses since both virus genomes and host genes are putative targets of viral sRNAs. The concept of RNA silencing is an elegant natural antiviral mechanism in plants. Viral sRNA-mediated regulation of gene expression is important in the frame of compatible interactions between plants and viruses.

Further reading: Recent Advances in Plant Virology | Virology Publications | RNA and the Regulation of Gene Expression

Antiviral Role of RNA Interference

from Michelle L. Flenniken, Mark Kunitomi, Michel Tassetto and Raul Andino in Insect Virology

Insects, like all living organisms, have developed defence mechanisms to resist infection. RNA interference (RNAi), a nucleic acid-based, post-transcriptional gene regulation process has recently emerged as a central pathway to anti-viral defence in insects. In this chapter, we outline the role of RNAi in insect immunity and highlight research that led to its discovery as well as research aimed at understanding the mechanistic details of anti-viral RNAi and the counter-measures viruses employ to modulate this immunological mechanism. As our knowledge of the pathways and mechanisms involved in insect immunity expands, so do the opportunities to employ insects as model systems to examine the general principles and co-evolution of hosts and their pathogens.

Further reading: Insect Virology

PDZ domains as sensors of other proteins

from Rebecca Kirk and Tim Clausen in Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition

Proteins containing PDZ domains have been shown to mediate a wide range of protein-protein interactions and to function as molecular scaffolds in the assembly of multi-protein complexes. The most studied typical function of PDZ domains is to recognize and bind short specific sequences at the C-terminal tails of their interacting partners; however other PDZ-mediated interactions including the recognition of internal motifs have been reported. PDZ domains are frequently combined with catalytic domains like, for example, protease, kinase and phosphatase domains. In this case, the PDZ domains do not simply function as molecular glue bringing entities of signaling cascades in contact with each other, but rather exert important regulatory functions by controlling the activity of their co-working partner domain. For one class of PDZ-enzymes, the HtrA proteases, the inter-domain communication has been studied in molecular detail providing the first insight into how PDZ domains control enzyme function and sense different external stimuli. HtrA proteins function to monitor protein homeostasis in the cell.

In prokaryotes this family of proteins underpins processes required for tolerance against various folding stresses and pathogenicity. Human HtrA proteins are involved in mammalian stress response pathways and in the prevention of the onset of protein misfolding diseases: including arthritis, Parkinson's and Alzheimer's disease. Recent biochemical and structural data indicate that the PDZ domains of HtrA proteins could act as sensors of folding stress, autoproteolysis, misfolded proteins, cleavage products and of specific interaction partners.

Further reading: Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition