October 7 - 9, 2010 Future Challenges in Food and Environmental Virology
Istanbul, Turkey Further information
2nd COST929 Symposium. A European Network for Environmental and Food Virology

Suggested reading: Environmental Microbiology Books

Key words: Environmental Virology

October 10 - 13, 2010 International Conference on Antivirals for Neglected and Emerging Viruses (ICAV-9)
Lubeck, Germany Further information
ICAV-9 will focus on the discovery of antiviral therapies of disease caused by dengue virus, influenza virus, enteroviruses, chikungunyavirus, coronaviruses, and other emerging or neglected viruses. Also have a microsymposium on Targeting Host Factors in HIV/AIDS Therapy

Suggested reading: Frontiers in Dengue Virus Research

Key words: Emerging Viruses | ICAV-9

from Philipe A.M. Gobeil and David A. Leib writing in Alphaherpesviruses: Molecular Virology:

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

Key words: Autophagy | Infection and immunity | Autophagy and the herpesviruses

from Christine M. Livingston, Christos Kyratsous, Saul Silverstein and Sandra K. Weller writing in Alphaherpesviruses: Molecular Virology:

Molecular chaperone proteins have long been recognized to play diverse and important roles in the life cycles of viruses from bacteriophage to SV40 to herpesviruses. The alphaherpesviruses HSV-1 and VZV not only interact with and reorganize cellular chaperones and co-chaperones but alphaherpesviruses also encode their own molecular chaperones. Cellular chaperones such as Hsp70, Hsc70 and Hsp90 are required for efficient production of infectious virus in that they play essential roles in nuclear transport of viral proteins, protein quality control and maintenance of cellular homeostasis during viral infection. These findings raise the possibility that molecular chaperones could be utilized as effective targets for antiviral therapy. A recent review reviews the evidence that replication of the human alphaherpesviruses herpes simplex virus type 1 and 2 (HSV-1 and 2) and varicella zoster virus (VZV) requires the activities of cellular and viral molecular chaperones.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: Alphaherpesvirus | Alphaherpesvirus Infection | Molecular Chaperones | Molecular chaperone proteins | Herpesviruses | Alphaherpesviruses | Molecular chaperone

from Paul T. Sobol and Karen L. Mossman writing in Alphaherpesviruses: Molecular Virology:

Key to the innate immune response to alpha herpesvirus infection is the expression and secretion of type I interferons (IFNs). This family of cytokines bolsters a host offensive to invading pathogens by inducing IFN stimulated genes (ISGs). Not surprisingly, the evolutionary pressure faced by alpha herpesviruses to adapt to the type I IFN response has shaped alpha herpesvirus evolution at the very interface of the virus-host interaction. The cumulative effects of type I IFN expression on alpha herpesvirus replication in vitro and dissemination in vivo are discussed in a recent review, along with mechanisms employed by these viruses to subvert the type I IFN response. Alpha herpesviruses block type I IFN production, inhibit the effects of type I IFN signal transduction and suppress downstream IFN-dependent effector pathways with the aims of augmenting viral replication and dissemination.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: Interferon | Interferon Responses | Herpesviruses | Alpha herpesvirus | Type I interferons | IFNs | Cytokines

from Samuel Rabkin writing in Alphaherpesviruses: Molecular Virology:

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

Key words: Oncolytic HSV | Cancer Therapy | Oncolytic HSV Vectors | HSV | oHSV | HSV Cancer Therapy | Virotherapy

I am pleased to provide the following excerpt from a book review of Neisseria: Molecular Mechanisms of Pathogenesis:

"an excellent, comprehensive and updated review ... The editors, both experienced in the Neisseria field, have recruited 43 contributors from five different countries. Many of these individuals are well-recognized experts, front-line researchers and/or key opinion leaders in their topics. They provide, evaluate and discuss detailed up-to-date understanding, the significance of different findings, theories, hypotheses and conclusions, and future directions in a research, clinical and public health perspective. The volume is valuable and timely ... Most chapters ... are excellent, comprehensive, important, updated, well-written, and contain many relevant references and informative figures/tables summarizing the key information ... the 'future trends' are valuably emphasized in most chapters. Some chapters even recommend good web resources for further reading ... the editors of the present volume have collated an impressive group of well-recognized experts that provide exceedingly interesting, comprehensive and up-to-date understanding regarding molecular mechanisms of pathogenesis in Neisseria, as well as an excellent bibliography for further reading. The volume is valuable, timely and can be highly recommended for researchers, microbiologists, molecular biologists, epidemiologists, clinicians, vaccine manufacturers and students, who are involved and/ or interested in any topic involving pathogenic Neisseria species." from Magnus Unemo (Orebro, Sweden) writing in Expert Rev. Anti Infect. Ther. (2010) 8: 871–875. read more ...

Neisseria: Molecular Mechanisms of Pathogenesis Edited by: Caroline Genco and Lee Wetzler ISBN: 978-1-904455-51-6 Publisher: Caister Academic Press Publication Date: January 2010 Cover: hardback "excellent, comprehensive ... valuable and timely ... highly recommended" (Expert Rev. Anti Infect. Ther.)

Key words: Neisseria | Neisseria Meningitidis | Meningitis | Meningococci | Meningococcus

from David C. Bloom and Dacia L. Kwiatkowski writing in Alphaherpesviruses: Molecular Virology:

Herpes simplex virus type 1 (HSV-1) latency is characterized by the persistence of viral genomes as episomes in the nuclei of sensory neurons. During this period only one region of the genome is abundantly transcribed: the region encoding the latency-associated transcripts (LATs). The LAT domain is transcriptionally complex, and while the predominant species that accumulates during latency is a 2.0 kb stable intron, other RNA species are transcribed from this region of the genome, including a number of lytic or acute-phase transcripts. In addition, a number of microRNA (miRNA) and non-miRNA small RNAs have recently been mapped to the LAT region of the genome. HSV-1 recombinant viruses with deletions of the LAT promoter exhibit reactivation deficits in a number of animal models, and there is evidence that other LAT deletion mutants also possess altered establishment and virulence properties. The phenotypic complexity associated with this region, as well as evidence that the LATs may play a role in suppressing latent gene expression, suggests that the LAT locus may function as a regulator to modulate the transcription of key lytic and latent genes.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: Herpes Simplex Virus | Alphaherpesvirus | Alphaherpesviruses | HSV | HSV-1 | HSV-1 Latency | LATS | Herpes simplex virus type 1 | Latency | LAT domain | MicroRNA | miRNAs

from Matthew D. Weitzman and Sandra K. Weller writing in Alphaherpesviruses: Molecular Virology:

The cellular DNA damage machinery responds to virus infection and the foreign genomes that accumulate in the nuclei of infected cells. Many DNA viruses have been shown to manipulate the cellular DNA damage response pathways in order to create environments conducive to their own replication. Some cellular factors are activated during infection while others are inactivated.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: HSV-1 | HSV-1 DNA Damage Response | DNA viruses | Alphaherpesvirus | Alphaherpesviruses | DNA damage response pathways

from Stacey A. Leisenfelder and Sandra K. Weller writing in Alphaherpesviruses: Molecular Virology:

The cis- and trans-acting elements required for DNA synthesis of Herpes Simplex Virus (HSV) have been identified, and genetic and biochemical analyses have provided important insights into how they work together to replicate the large double-stranded viral genome. Furthermore, viral enzymes involved in DNA replication have provided a rich store of useful targets for antiviral therapy against herpesviruses. Despite these advances, many questions remain unresolved concerning the overall mechanism of genome replication. For instance, it has long been recognized that the products of viral DNA replication are head-to-tail concatemers; however, it is not clear how these concatemers are generated. A recent review summarizes the known functions of viral replication proteins and explore the possibility that these viral proteins may function in combination with cellular proteins to produce concatemers suitable for packaging into preformed viral capsids.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: HSV | HSV Replication | HSV-1 Replication | Herpes Simplex Virus | Herpesvirus | HSV-1 | HSV-1 DNA Replication

from Stephen A. Rice writing in Alphaherpesviruses: Molecular Virology:

ICP22 is the least characterized of the five herpes simplex virus type 1 (HSV-1) immediate-early (IE) proteins. However, accumulating evidence indicates that it carries out a number of interesting regulatory activities inside the infected cell. These include the enhancement of viral gene expression, the modification of RNA polymerase II (RNAP II), and the reorganization of host cell molecular chaperones into nuclear inclusion bodies. Recent studies of engineered HSV-1 mutants indicate that certain of ICP22's activities are genetically separable from each other. Thus, similar to several other of the IE proteins, ICP22 appears to be a multifunctional, multi-domain polypeptide. A recent review summarizes the current state of knowledge concerning ICP22 and its varied regulatory roles during the productive HSV-1 infection.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: HSV | HSV-1 Replication | ICP22 | HSV ICP22 | HSV RNA polymerase II | HSV-1 Immediate-early proteins

from Roger D. Everett writing in Alphaherpesviruses: Molecular Virology:

In recent years it has become apparent that, in addition to the acquired and innate defences against virus infection, there is also a third aspect to antiviral defences that operates at the intracellular level. This concept is known as intrinsic resistance, intrinsic antiviral defence or intrinsic immunity. Its key features include constitutively expressed cellular proteins that restrict viral gene expression, and viral regulatory proteins that counteract the actions of the cellular inhibitors. A recent review reviews the cellular proteins and pathways that are thought to be involved in intrinsic resistance to HSV-1 infection, and the mechanisms by which these are inactivated by ICP0, an important viral regulatory protein. The phenotype of ICP0 null mutant HSV-1 is described to give a background to the phenomenon, then the principal properties of ICP0 itself are summarised. The effects of ICP0 on components of cellular nuclear structures known as ND10 or PML nuclear bodies are reviewed, then the possible roles of these proteins in intrinsic resistance are discussed. The relationships between ICP0, intrinsic resistance and the regulation of viral chromatin structure are considered, and finally the parallels between ICP0 and related proteins expressed by other alphaherpesviruses are described. Intrinsic resistance and the manner in which viruses overcome it are important aspects of the biology of virus infection, but we have much to learn before we achieve a complete understanding of the viral and cellular proteins that are involved.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: Alphaherpesviruses | Alphaherpesvirus | HSV | HSV-1 infection | Resistance to HSV | HSV-1 Resistance

from Rozanne M. Sandri-Goldin writing in Alphaherpesviruses: Molecular Virology:

Herpes simplex virus 1 (HSV-1) protein ICP27 is a multifunctional regulator that is essential for HSV-1 infection. ICP27 performs a number of different functions during infection that include inhibiting cellular pre-mRNA splicing, stimulating viral early and late gene transcription by recruiting cellular RNA polymerase II to viral replication sites, binding and exporting viral RNA to the cytoplasm and stimulating translation of some HSV-1 transcripts by binding translation initiation factors. ICP27 also recruits Hsc70 to nuclear foci (VICE domains) that are enriched in chaperones and components of the proteasome, and which are believed to be involved in nuclear protein quality control. ICP27 interacts with a number of proteins and it binds RNA. Post-translational modifications have been demonstrated to regulate ICP27's interactions with several proteins. NMR analysis of the N-terminus showed that it is highly flexible, which may be necessary for switching between different protein interactions. Further, ICP27 undergoes a head-to-tail intramolecular association that may also regulate its interactions, especially with proteins that require that both the N- and C-termini of ICP27 be intact for interaction. A recent review covers the different activities of ICP27 and what we know about how these activities are regulated.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: Multifunctional regulator | ICP27 | ICP27 Multifunctional regulator | HSV-1 infection

from Keith R. Jerome writing in Alphaherpesviruses: Molecular Virology:

HSV presents unique challenges to the human immune system. Most of these result from the ability of the virus to establish latency in neurons of the dorsal root ganglia. The first line of defense against the initial establishment of latent infection is the innate immune response. The innate response relies on a variety of cell types recognizing HSV infection via pattern recognition receptors, including toll-like receptors. After exposure, the adaptive immune response is triggered. However, the adaptive response must deal with reactivation of HSV from the latently infected neuron, which in turn seeds mucosal sites with virus. T cells are especially important in this, and likely control both the extent of reactivation from latently infected neurons as well as the extent of viral replication at mucosal sites. Not surprising, HSV has evolved a wide variety of immune evasion mechanisms to tip this balance in its favor and facilitate transmission to new hosts. The study of HSV and its interaction with the host immune system has provided insights into the function of both, and may ultimately facilitate the development of an effective HSV vaccine.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: Herpes Simplex Virus | Herpes virus | Herpes viruses | Herpesvirus | Herpesviruses

from Timothy E. Dudek and David M. Knipe writing in Alphaherpesviruses: Molecular Virology:

Vaccines have been among the most effective public health approaches for protecting individuals against viral disease, with two of the world's most successful vaccines being against smallpox virus and poliovirus. Herpes simplex virus 1 (HSV-1) is a nearly ubiquitous pathogen, and the worldwide prevalence of herpes simplex virus 2 (HSV-2) continues to increase. These two pathogens cause significant morbidity and mortality among the general population, but in particular in neonates and immunocompromised individuals. Perhaps most significantly, there is a 3-4 fold increased risk of HIV acquisition in HSV-2 infected individuals. To date, attempts at producing a vaccine against HSV have not been successful, but each attempt has brought insights into what may be required for an effective vaccine. Furthermore, intense studies into the immunology of HSV infection and the resources that have been put into vaccine design and development have recently yielded knowledge that will be necessary to achieve the goal of a highly effective vaccine against HSV.

Further reading: Alphaherpesviruses: Molecular Virology

Key words: HSV | Herpes Simplex Virus | Herpes virus | Herpes viruses | Smallpox virus | Poliovirus | Herpesvirus | Herpesviruses