Epigenetics
Epigenetics, a term that refers to cellular mechanisms that confer stability of gene expression during development, is a rapidly advancing field of biological and medical research. The main molecular mechanisms that mediate epigenetic phenomena are DNA methylation and chromatin modifications.
Bacteria, as well as eukaryotes, make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. However, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of various pathogenic bacteria including Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression.
Epigenetic regulation can enable unicellular organisms to respond rapidly to environmental stresses or signals. For example, the yeast prion PSI is generated by a conformational change of the Sup35p translation termination factor, which is then inherited by daughter cells. This can provide a survival advantage under adverse conditions.
Prions can be defined by their ability to catalytically convert other native state versions of the same protein to an infectious conformational state. In this sense they can be viewed as epigenetic agents capable of inducing a phenotypic change without a modification of the genome.
Further reading Epigenetics
Bacteria, as well as eukaryotes, make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. However, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of various pathogenic bacteria including Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression.
Epigenetic regulation can enable unicellular organisms to respond rapidly to environmental stresses or signals. For example, the yeast prion PSI is generated by a conformational change of the Sup35p translation termination factor, which is then inherited by daughter cells. This can provide a survival advantage under adverse conditions.
Prions can be defined by their ability to catalytically convert other native state versions of the same protein to an infectious conformational state. In this sense they can be viewed as epigenetic agents capable of inducing a phenotypic change without a modification of the genome.
Further reading Epigenetics
Acinetobacter Molecular Biology: Book review
The editor of the book Acinetobacter Molecular Biology, Ulrike Gerischer from the University of Ulm, Germany, has succeeded in finding competent authors to write about different aspects of the genus Acinetobacter. Acinetobacter, of the order Pseudomonadales and belonging to the gamma-Proteobacteria, comprise a group of microorganisms from soil and water, which contribute to mineralization of, for example, aromatic compounds. As the name implies, they are non-motile. Through their resistance to many classes of antibiotics, they also cause infections especially in a hospital environment.
In Chapter one, the diversity of the genus Acinetobacter is described. The chapter starts with taxonomy, which is regarded as complicated and chaotic for this genus. Additionally, a box with comprehensive information about taxonomy practices is very helpful. The following part of this chapter describes very clearly different identification methods, mainly PCR-based fingerprtinting methods. Taxonomy is also the one subject of the 2nd chapter, which stresses its importance especially for the discussed genus. The suitability of using the 16S rRNA gene for identification is construed. Unfortunately, this interesting subject is not written in the best English. Additionally, sentences are sometimes to long, which makes it difficult to comprehend. The catabolism of aromatic compounds in Acinetobacter is very briefly discussed in Chapter four.
The most important species of the genus is A. baylyi, which is reflected by the fact that four chapters deal almost exclusively with that species. The strain is very much appreciated as research tool for scientists, long before the genome of A. baylyi ADP1 was completely sequenced in 2004. One of the most important features is its natural transformation mechanism (Chapter five). The highly effective competence of A. baylyi makes it a very valuable research tool. Different aspects of transformation such as physiology, genetic analysis, transcriptional regulation etc. are explained in a very descriptive way. The subject of transformation comes briefly back in Chapter six, which is dedicated to Genetics. A brief overview of aspects of the A. baylyi genome and tools for genetic engineering is given. The following two chapters (Chapters seven and eight) detail information about LysR-type transcriptional regulators and the beta-ketoadipate pathway.
In Chapter nine, the different applications of Acinetobacter in biotechnology are construed. These applications are, besides others, biodegradation, bioremediation, novel lipid and peptide production and biosurfactant production. A summary of this chapter would have been helpful.
The biomedical importance of Acinetobacter is reflected in Chapters three, ten, eleven and twelve. In Chapter three lipoplysaccharides are extensively reviewed, including its contribution to bacterial virulence. The molecular basis of virulence and pathogenicity is dealed with in Chapter ten, of which the most part is about biofilm formation. In the following chapter (Chapter eleven) the epidemiology of Acinetobacter is reviewed. Various typing methods are briefly explained, which have been partly discussed in Chapter one. Antibiotic resistance is the subject of Chapter twelve. Besides others, multidrug resistance and the different classes of antibiotics are described.
The book covers a broad range of interesting and important aspects of the moleclar biology of Acinetobacter. It is mainly written for specialists in the area of Acinetobacter. Today, even for this readership, it is almost impossible to cite all avaliable literature. Therefore, this book comes in handy with all gathered information about the molecular biology of Acinetobacter. Each chapter contains an extensive reference list, up-to-date and ample appropriate diagrams and tables. A separate section about future aspects at the end of four of the twelve chapters and also the index at the end of the book are very much appreciated.
Overall, this book is a valuable contribution to the literature and suitable to anyone involved in Acinetobacter research. The price of the book is somewhat expensive.
Review by: Mareike Viebahn, PhD, Centocor BV, Einsteinweg 92, 2333 CD Leiden, The Netherlands
Full details of the book available at Acinetobacter Molecular Biology
In Chapter one, the diversity of the genus Acinetobacter is described. The chapter starts with taxonomy, which is regarded as complicated and chaotic for this genus. Additionally, a box with comprehensive information about taxonomy practices is very helpful. The following part of this chapter describes very clearly different identification methods, mainly PCR-based fingerprtinting methods. Taxonomy is also the one subject of the 2nd chapter, which stresses its importance especially for the discussed genus. The suitability of using the 16S rRNA gene for identification is construed. Unfortunately, this interesting subject is not written in the best English. Additionally, sentences are sometimes to long, which makes it difficult to comprehend. The catabolism of aromatic compounds in Acinetobacter is very briefly discussed in Chapter four.
The most important species of the genus is A. baylyi, which is reflected by the fact that four chapters deal almost exclusively with that species. The strain is very much appreciated as research tool for scientists, long before the genome of A. baylyi ADP1 was completely sequenced in 2004. One of the most important features is its natural transformation mechanism (Chapter five). The highly effective competence of A. baylyi makes it a very valuable research tool. Different aspects of transformation such as physiology, genetic analysis, transcriptional regulation etc. are explained in a very descriptive way. The subject of transformation comes briefly back in Chapter six, which is dedicated to Genetics. A brief overview of aspects of the A. baylyi genome and tools for genetic engineering is given. The following two chapters (Chapters seven and eight) detail information about LysR-type transcriptional regulators and the beta-ketoadipate pathway.
In Chapter nine, the different applications of Acinetobacter in biotechnology are construed. These applications are, besides others, biodegradation, bioremediation, novel lipid and peptide production and biosurfactant production. A summary of this chapter would have been helpful.
The biomedical importance of Acinetobacter is reflected in Chapters three, ten, eleven and twelve. In Chapter three lipoplysaccharides are extensively reviewed, including its contribution to bacterial virulence. The molecular basis of virulence and pathogenicity is dealed with in Chapter ten, of which the most part is about biofilm formation. In the following chapter (Chapter eleven) the epidemiology of Acinetobacter is reviewed. Various typing methods are briefly explained, which have been partly discussed in Chapter one. Antibiotic resistance is the subject of Chapter twelve. Besides others, multidrug resistance and the different classes of antibiotics are described.
The book covers a broad range of interesting and important aspects of the moleclar biology of Acinetobacter. It is mainly written for specialists in the area of Acinetobacter. Today, even for this readership, it is almost impossible to cite all avaliable literature. Therefore, this book comes in handy with all gathered information about the molecular biology of Acinetobacter. Each chapter contains an extensive reference list, up-to-date and ample appropriate diagrams and tables. A separate section about future aspects at the end of four of the twelve chapters and also the index at the end of the book are very much appreciated.
Overall, this book is a valuable contribution to the literature and suitable to anyone involved in Acinetobacter research. The price of the book is somewhat expensive.
Review by: Mareike Viebahn, PhD, Centocor BV, Einsteinweg 92, 2333 CD Leiden, The Netherlands
Full details of the book available at Acinetobacter Molecular Biology
Staphylococcus: hospital and community-acquired infection
The staphylococci are important pathogenic bacteria responsible for a variety of diseases in humans and other animals. They are the most common cause of hospital acquired infection and antibiotic resistant strains (MRSA) have become endemic in hospitals in most countries causing major public health issues. In addition, the incidence of new strains that cause severe community-acquired infections in healthy people is increasing and MRSA strains are emerging in agricultural and domestic animals. In the race to understand staphylococcal pathogenesis the focus has been on genetics, as a bacterium can only do what its genes allow. The publication of the first staphylococcal whole genome sequence in 2001 paved the way for a greater understanding of the molecular basis of its virulence, evolution, epidemiology and drug resistance. Since then the available genomic data has mushroomed and this, coupled with the major advances in genetic know-how and the availability of better genetic tools, has allowed significant advances to be made.
More information ...
Available in early 2008, a new book focuses on staphylococcal genetics, bringing together the expertise and enthusiasm of an international panel of leading staphylococcal researchers and providing a state-of-the art overview of the field.
Staphylococcus: Molecular Genetics
More information ...
Available in early 2008, a new book focuses on staphylococcal genetics, bringing together the expertise and enthusiasm of an international panel of leading staphylococcal researchers and providing a state-of-the art overview of the field.
Staphylococcus: Molecular Genetics
Cyanobacteria: Book review
The Cyanobacteria: Molecular Biology, Genomics and Evolution
This book is one of the most comprehensive collections of articles dealing with Cyanobacteria, presenting the current knowledge of these fascinating, yet still underinvestigated group of procaryotic organisms. The focus of its sixteen chapters is strongly on the molecular, physiological and ecophysiological side, but with some articles dealing with Environmental and Comparative Genomics. This might be a bit disappointing for readers more interested in the morphology and systematics of Cyanobacteria - both topics that are not at all or only barely touched, but it also truly reflects our current lack of knowledge about the phylogeny and the evolutionary history in this group.
For taxonomists and morphologists, as well as phylogeneticists, this volume might be of lesser interest. However, the book can be highly recommended as a useful compilation of review articles for scientists in the field, but also for graduate students who will benefit from an introduction into the molecular biology, molecular ecology, and physiology of Cyanobacteria.
Review by: Prof. Dr. Frank Kauff, Kaiserslautern University, Germany
Full details of the book available at The Cyanobacteria: Molecular Biology, Genomics and Evolution
This book is one of the most comprehensive collections of articles dealing with Cyanobacteria, presenting the current knowledge of these fascinating, yet still underinvestigated group of procaryotic organisms. The focus of its sixteen chapters is strongly on the molecular, physiological and ecophysiological side, but with some articles dealing with Environmental and Comparative Genomics. This might be a bit disappointing for readers more interested in the morphology and systematics of Cyanobacteria - both topics that are not at all or only barely touched, but it also truly reflects our current lack of knowledge about the phylogeny and the evolutionary history in this group.
For taxonomists and morphologists, as well as phylogeneticists, this volume might be of lesser interest. However, the book can be highly recommended as a useful compilation of review articles for scientists in the field, but also for graduate students who will benefit from an introduction into the molecular biology, molecular ecology, and physiology of Cyanobacteria.
Review by: Prof. Dr. Frank Kauff, Kaiserslautern University, Germany
Full details of the book available at The Cyanobacteria: Molecular Biology, Genomics and Evolution
Virology books
A list of 10 recent virology books. These are aimed at research scientists, graduate students, medical reseachers and other professionals and are highly recommended for all virology/microbiology libraries.
Further information
Full details
Further information
 | Animal Viruses: Molecular Biology |
| Edited by: Thomas C. Mettenleiter and Francisco Sobrino ISBN: 978-1-904455-22-6 Publisher: Caister Academic Press Publication Date: January 2008 Cover: Hardback | |
 | Segmented Double-Stranded RNA Viruses: Structure and Molecular Biology |
| Edited by: John T. Patton ISBN: 978-1-904455-21-9 Publisher: Caister Academic Press Publication Date: January 2008 Cover: Hardback | |
 | Coronaviruses: Molecular and Cellular Biology |
| Edited by: Volker Thiel ISBN: 978-1-904455-16-5 Publisher: Caister Academic Press Publication Date: August 2007 Cover: Hardback | |
 | Bacteriophage: Genetics and Molecular Biology |
| Edited by: Stephen Mc Grath and Douwe van Sinderen ISBN: 978-1-904455-14-1 Publisher: Caister Academic Press Publication Date: July 2007 Cover: Hardback | |
 | Alpha Herpesviruses: Molecular and Cellular Biology |
| Edited by: R. M. Sandri-Goldin ISBN: 978-1-904455-09-7 Publisher: Caister Academic Press Publication Date: August 2006 Cover: Hardback | |
 | AIDS Vaccine Development: Challenges and Opportunities |
| Edited by: Wayne Koff, Patricia Kahn and Ian D. Gust ISBN: 978-1-904455-11-0 Publisher: Caister Academic Press Publication Date: February 2007 Cover: Paperback | |
 | Influenza Virology: Current Topics |
| Edited by: Yoshihiro Kawaoka ISBN: 978-1-904455-06-6 Publisher: Caister Academic Press Publication Date: March 2006 Cover: Hardback | |
 | Cytomegaloviruses: Molecular Biology and Immunology |
| Edited by: Matthias J. Reddehase ISBN: 978-1-904455-02-8 Publisher: Caister Academic Press Publication Date: January 2006 Cover: Hardback | |
 | Papillomavirus Research: From Natural History To Vaccines and Beyond |
| Edited by: M. Saveria Campo ISBN: 978-1-904455-04-2 Publisher: Caister Academic Press Publication Date: January 2006 Cover: Hardback | |
 | Epstein-Barr Virus |
| Edited by: Erle S. Robertson ISBN: 978-1-904455-03-5 Publisher: Caister Academic Press Publication Date: September 2005 Cover: Hardback |
Full details
Focus on Animal Viruses
The study of animal viruses is important from a veterinary viewpoint and many of these viruses cause diseases that are economically devastating. Many animal viruses are also important from a human medical perspective. The emergence of the SARS virus in the human population, coming from an animal source, highlights the importance of animals in harbouring infectious agents; avian influenza viruses can directly infect humans. In addition research into animal viruses has made an important contribution to our understanding of viruses in general, their replication, molecular biology, evolution and interaction with the host.
Foot-and-Mouth Disease Virus
Foot-and-mouth disease virus (FMDV) is the prototypic member of the Aphthovirus genus in the Picornaviridae family. This picornavirus is the etiological agent of an acute systemic vesicular disease that affects cattle worldwide. FMDV is a highly variable and transmissible virus. Soon after infection, the single stranded positive RNA that constitutes the viral genome is efficiently translated using a cap-independent mechanism driven by the internal ribosome entry site element (IRES). This process occurs concomitantly with the inhibition of cellular protein synthesis, caused by the expression of viral proteases. Processing of the viral polyprotein is achieved cotranslationally by viral encoded proteases, giving rise to the different mature viral proteins. Viral RNA as well as viral proteins interact with different components of the host cell, acting as key determinants of viral pathogenesis. In depth knowledge of the molecular basis of the viral cycle is needed to control viral pathogenesis and disease spreading.
More info: Animal Viruses: Molecular Biology
Pestiviruses
Pestiviruses account for important diseases in animals such as Classical swine fever (CSF) and Bovine viral diarrhea / Mucosal disease (BVD/MD). According to the current O.I.E. list CSF and BVD/MD are notifiable diseases and eradication programms are administered in many countries worldwide. The molecular biology of pestiviruses shares many similarities and peculiarities with the human hepaciviruses. Genome organisation and translation strategy are highly similar for the members of both genera. One hallmark of pestiviruses is their unique strategy to establish persistent infection during pregnancy. Persistent infection with pestiviruses often goes unnoticed; for BVDV frequently nonhomologous RNA recombination events lead to the appearance of genetically distinct viruses that are lethal to the host.
More info: Animal Viruses: Molecular Biology
Arteriviruses
In 1996, the family Arteriviridae was included within the order Nidovirales. Arteriviruses are small, enveloped, animal viruses with an icosahedral core containing a positive-sense RNA genome. The family includes equine arteritis virus (EAV), porcine reproductive and respiratory syndrome virus (PRRSV), lactate dehydrogenaseelevating virus (LDV) of mice and simian hemorrhagic fever virus (SHFV). Three of these viruses were first discovered and characterized a in 1964 (EAV-1953, LDV-1960 and SHFV), whereas PRRSV was first isolated in Europe and in North America in the early 1990s. The arteriviruses are highly species specific, but share many biological and molecular properties, including virion morphology, a unique set of structural proteins, genome organization and replication strategy, and the ability to establish prolonged or true persistent infection in their natural hosts. However, the epidemiology and pathogenesis of the infection caused by each virus is distinct, as are the diseases they cause.
More info: Animal Viruses: Molecular Biology
Coronaviruses
Coronavirus (CoV) genome replication takes place in the cytoplasm in a membrane-protected microenvironment, and starts with the translation of the genome to produce the viral replicase. CoV transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. The requirement for basepairing during transcription has been formally demonstrated in arteriviruses and CoVs. CoV N protein is required for coronavirus RNA synthesis, and has RNA chaperone activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. CoVs initiate translation by cap-dependent and capindependent mechanisms. Cell macromolecular synthesis may be controlled after CoV infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation, and immune and stress responses. The balance between genes up- and down-regulated could explain the pathogenesis caused by these viruses. Coronavirus expression systems based on single genome constructed by targeted recombination, or by using infectious cDNAs, have been developed. The possibility of expressing different genes under the control of transcription regulating sequences (TRSs) with programmable strength, and engineering tissue and species tropism indicates that CoV vectors are flexible. CoV based vectors have emerged with high potential for vaccine development and, possibly, for gene therapy.
More info: Coronaviruses: Molecular and Cellular Biology
Hendra and Nipah Virus
Over the past decade, the previously unknown paramyxoviruses Hendra virus (HeV) and Nipah virus (NiV) have emerged in humans and livestock in Australia and Southeast Asia. Both viruses are contagious, highly virulent, and capable of infecting a number of mammalian species and causing potentially fatal disease. Due to the lack of a licensed vaccine or antiviral therapies, HeV and NiV are designated as biosafety level (BSL) 4 agents. The genomic structure of both viruses is that of a typical paramyxovirus. However, due to limited sequence homology and little immunological cross-reactivity with other paramyxoviruses, HeV and NiV have been classified into a new genus within the family Paramyxoviridae named Henipavirus.
More info: Animal Viruses: Molecular Biology
Avian Influenza
Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally viruses are transmitted from this reservoir to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. Proteolytic activation of the hemagglutinin is an important determinant for pathogenicity and adaptation of the receptor binding specificity of the hemagglutinin and adaptation of the polymerase to new hosts play important roles in interspecies transmission.
More info: Influenza Virology: Current Topics
Bluetongue Virus
Bluetongue virus (BTV), a member of Orbivirus genus within the Reoviridae family causes serious disease in livestock (sheep, goat, cattle). Partly due to this BTV has been in the forefront of molecular studies for last three decades and now represents one of the best understood viruses at the molecular and structural levels. BTV, like the other members of the family is a complex non-enveloped virus with seven structural proteins and a RNA genome consisting of 10 double-stranded (ds) RNA segments of different sizes. It has been possible to determine the complex nature of the virion through 3D structure reconstructions (diameter ~ 800 Å); the atomic structure of proteins and the internal capsid (~ 700 Å, the first large highly complex structure ever solved); the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell and the protein sequestration required for it; and the role of host proteins in virus entry and virus release. These areas are important for BTV replication but they also indicate the pathways that may be used by related viruses, which include viruses that are pathogenic to man and animals, thus providing the basis for developing strategies for intervention or prevention.
More info: Segmented Double-stranded RNA Viruses
Porcine Circoviruses
Porcine Circoviruses (PCV) are the smallest viruses replicating autonomously in eukaryotic cells. The virions are non-enveloped and spherical with a diameter of 16-18 nm and the covalently closed and single-stranded DNA genomes comprise less than 1800 nucleotides. The genomes encode only two major open reading frames. The gene products Rep, Rep' and Cap are involved in viral replication, regulation of transcription and capsid formation. Due to their highly limited coding capacity, circoviruses are supposed to rely principally on the host's machinery for synthesis of macromolecules. Two types of PCV are known, which differ with respect to their pathogenicity. Porcine circovirus type 1 (PCV1) is not linked with a disease, while porcine circovirus type 2 (PCV2) is the etiological agent of Postweaning Multisystemic Wasting Syndrome (PMWS), a new emerging and multifactorial disease in swine. PCV1 and PCV2 show a high degree of sequence homology and a similar genomic organisation; nevertheless, the basis of the distinct pathogenicity has not yet been unravelled.
More info: Animal Viruses: Molecular Biology
Herpesviruses
Herpesviruses are highly successful pathogens infecting animals and man. Although there is a wide variety of different herpesviruses with different biological characteristics, they have in common basic properties such as morphology of the virion, highly regulated transcription and establishment of latency. In animal virology the most important herpesviruses belong to the Alphaherpesvirinae. Research on pseudorabies virus, the causative agent of Aujeszky's disease in pigs, has pioneered animal disease control with genetically modified vaccines. PrV is now extensively studied as a model for basic processes during lytic herpesvirus infection, and for unravelling molecular mechanisms of herpesvirus neurotropism, whereas bovine herpesvirus 1, the causative agent of bovine infectious rhinotracheitis and pustular vulvovaginitis, is analyzed to elucidate molecular mechanisms of latency. The avian infectious laryngotracheitis virus is phylogenetically distant from these two viruses and serves to underline similarity and diversity within the Alphaherpesvirinae.
More info: Alpha Herpesviruses: Molecular and Cellular Biology
African Swine Fever Virus
African swine fever virus (ASFV) is a large double-stranded DNA virus which replicates in the cytoplasm of infected cells and is the only member of the Asfarviridae family. In common with other viral haemorrhagic fevers, the main target cells for replication are those of monocyte, macrophage lineage. The virus causes a haemorrhagic fever with high mortality rates in pigs, but persistently infects its natural hosts, warthogs, bushpigs and soft ticks of the Ornithodoros species with no disease signs. The virus encodes enzymes required for replication and transcription of the genome, including elements of a base excision repair system, structural proteins and many proteins that are not essential for replication in cells but have roles in virus survival and transmission in its hosts. Virus replication takes place in perinuclear factory areas. Assembly of the icosahedral capsid occurs on modified membranes from the endoplasmic reticulum. Products from proteolytically processed polyproteins form the core shell between the internal membrane and the nucleoprotein core. An additional outer membrane is gained as particles bud from the plasma membrane. The virus encodes proteins that inhibit signalling pathways in infected macrophages and thus modulate transcriptional activation of immune response genes. In addition the virus encodes proteins which inhibit apoptosis of infected cells to facilitate production of progeny virions. Viral membrane proteins with similarity to cellular adhesion proteins modulate interaction of virus-infected cells and extracellular virions with host components.
More info: Animal Viruses: Molecular Biology
Featured book: Animal Viruses: Molecular Biology Edited by: Thomas C. Mettenleiter and Francisco Sobrino In this book an international panel of leading virologists provide a state-of-the-art overview of the field, comprehensively detailing the current understanding of viruses, their replication, evolution and interaction with the host. The authors emphasize strategic and methodological aspects of current research, and provide key related references. Topics include foot-and-mouth disease virus, Pestivirus, Arteriviridae, Coronaviruses (including SARS), Herpesviridae, Paramyxoviridae, influenza viruses, Reoviridae, porcine circoviruses, Asfarviridae and much more. An essential text for all virology laboratories.
Foot-and-Mouth Disease Virus
Foot-and-mouth disease virus (FMDV) is the prototypic member of the Aphthovirus genus in the Picornaviridae family. This picornavirus is the etiological agent of an acute systemic vesicular disease that affects cattle worldwide. FMDV is a highly variable and transmissible virus. Soon after infection, the single stranded positive RNA that constitutes the viral genome is efficiently translated using a cap-independent mechanism driven by the internal ribosome entry site element (IRES). This process occurs concomitantly with the inhibition of cellular protein synthesis, caused by the expression of viral proteases. Processing of the viral polyprotein is achieved cotranslationally by viral encoded proteases, giving rise to the different mature viral proteins. Viral RNA as well as viral proteins interact with different components of the host cell, acting as key determinants of viral pathogenesis. In depth knowledge of the molecular basis of the viral cycle is needed to control viral pathogenesis and disease spreading.
More info: Animal Viruses: Molecular Biology
Pestiviruses
Pestiviruses account for important diseases in animals such as Classical swine fever (CSF) and Bovine viral diarrhea / Mucosal disease (BVD/MD). According to the current O.I.E. list CSF and BVD/MD are notifiable diseases and eradication programms are administered in many countries worldwide. The molecular biology of pestiviruses shares many similarities and peculiarities with the human hepaciviruses. Genome organisation and translation strategy are highly similar for the members of both genera. One hallmark of pestiviruses is their unique strategy to establish persistent infection during pregnancy. Persistent infection with pestiviruses often goes unnoticed; for BVDV frequently nonhomologous RNA recombination events lead to the appearance of genetically distinct viruses that are lethal to the host.
More info: Animal Viruses: Molecular Biology
Arteriviruses
In 1996, the family Arteriviridae was included within the order Nidovirales. Arteriviruses are small, enveloped, animal viruses with an icosahedral core containing a positive-sense RNA genome. The family includes equine arteritis virus (EAV), porcine reproductive and respiratory syndrome virus (PRRSV), lactate dehydrogenaseelevating virus (LDV) of mice and simian hemorrhagic fever virus (SHFV). Three of these viruses were first discovered and characterized a in 1964 (EAV-1953, LDV-1960 and SHFV), whereas PRRSV was first isolated in Europe and in North America in the early 1990s. The arteriviruses are highly species specific, but share many biological and molecular properties, including virion morphology, a unique set of structural proteins, genome organization and replication strategy, and the ability to establish prolonged or true persistent infection in their natural hosts. However, the epidemiology and pathogenesis of the infection caused by each virus is distinct, as are the diseases they cause.
More info: Animal Viruses: Molecular Biology
Coronaviruses
Coronavirus (CoV) genome replication takes place in the cytoplasm in a membrane-protected microenvironment, and starts with the translation of the genome to produce the viral replicase. CoV transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. The requirement for basepairing during transcription has been formally demonstrated in arteriviruses and CoVs. CoV N protein is required for coronavirus RNA synthesis, and has RNA chaperone activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. CoVs initiate translation by cap-dependent and capindependent mechanisms. Cell macromolecular synthesis may be controlled after CoV infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation, and immune and stress responses. The balance between genes up- and down-regulated could explain the pathogenesis caused by these viruses. Coronavirus expression systems based on single genome constructed by targeted recombination, or by using infectious cDNAs, have been developed. The possibility of expressing different genes under the control of transcription regulating sequences (TRSs) with programmable strength, and engineering tissue and species tropism indicates that CoV vectors are flexible. CoV based vectors have emerged with high potential for vaccine development and, possibly, for gene therapy.
More info: Coronaviruses: Molecular and Cellular Biology
Hendra and Nipah Virus
Over the past decade, the previously unknown paramyxoviruses Hendra virus (HeV) and Nipah virus (NiV) have emerged in humans and livestock in Australia and Southeast Asia. Both viruses are contagious, highly virulent, and capable of infecting a number of mammalian species and causing potentially fatal disease. Due to the lack of a licensed vaccine or antiviral therapies, HeV and NiV are designated as biosafety level (BSL) 4 agents. The genomic structure of both viruses is that of a typical paramyxovirus. However, due to limited sequence homology and little immunological cross-reactivity with other paramyxoviruses, HeV and NiV have been classified into a new genus within the family Paramyxoviridae named Henipavirus.
More info: Animal Viruses: Molecular Biology
Avian Influenza
Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally viruses are transmitted from this reservoir to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. Proteolytic activation of the hemagglutinin is an important determinant for pathogenicity and adaptation of the receptor binding specificity of the hemagglutinin and adaptation of the polymerase to new hosts play important roles in interspecies transmission.
More info: Influenza Virology: Current Topics
Bluetongue Virus
Bluetongue virus (BTV), a member of Orbivirus genus within the Reoviridae family causes serious disease in livestock (sheep, goat, cattle). Partly due to this BTV has been in the forefront of molecular studies for last three decades and now represents one of the best understood viruses at the molecular and structural levels. BTV, like the other members of the family is a complex non-enveloped virus with seven structural proteins and a RNA genome consisting of 10 double-stranded (ds) RNA segments of different sizes. It has been possible to determine the complex nature of the virion through 3D structure reconstructions (diameter ~ 800 Å); the atomic structure of proteins and the internal capsid (~ 700 Å, the first large highly complex structure ever solved); the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell and the protein sequestration required for it; and the role of host proteins in virus entry and virus release. These areas are important for BTV replication but they also indicate the pathways that may be used by related viruses, which include viruses that are pathogenic to man and animals, thus providing the basis for developing strategies for intervention or prevention.
More info: Segmented Double-stranded RNA Viruses
Porcine Circoviruses
Porcine Circoviruses (PCV) are the smallest viruses replicating autonomously in eukaryotic cells. The virions are non-enveloped and spherical with a diameter of 16-18 nm and the covalently closed and single-stranded DNA genomes comprise less than 1800 nucleotides. The genomes encode only two major open reading frames. The gene products Rep, Rep' and Cap are involved in viral replication, regulation of transcription and capsid formation. Due to their highly limited coding capacity, circoviruses are supposed to rely principally on the host's machinery for synthesis of macromolecules. Two types of PCV are known, which differ with respect to their pathogenicity. Porcine circovirus type 1 (PCV1) is not linked with a disease, while porcine circovirus type 2 (PCV2) is the etiological agent of Postweaning Multisystemic Wasting Syndrome (PMWS), a new emerging and multifactorial disease in swine. PCV1 and PCV2 show a high degree of sequence homology and a similar genomic organisation; nevertheless, the basis of the distinct pathogenicity has not yet been unravelled.
More info: Animal Viruses: Molecular Biology
Herpesviruses
Herpesviruses are highly successful pathogens infecting animals and man. Although there is a wide variety of different herpesviruses with different biological characteristics, they have in common basic properties such as morphology of the virion, highly regulated transcription and establishment of latency. In animal virology the most important herpesviruses belong to the Alphaherpesvirinae. Research on pseudorabies virus, the causative agent of Aujeszky's disease in pigs, has pioneered animal disease control with genetically modified vaccines. PrV is now extensively studied as a model for basic processes during lytic herpesvirus infection, and for unravelling molecular mechanisms of herpesvirus neurotropism, whereas bovine herpesvirus 1, the causative agent of bovine infectious rhinotracheitis and pustular vulvovaginitis, is analyzed to elucidate molecular mechanisms of latency. The avian infectious laryngotracheitis virus is phylogenetically distant from these two viruses and serves to underline similarity and diversity within the Alphaherpesvirinae.
More info: Alpha Herpesviruses: Molecular and Cellular Biology
African Swine Fever Virus
African swine fever virus (ASFV) is a large double-stranded DNA virus which replicates in the cytoplasm of infected cells and is the only member of the Asfarviridae family. In common with other viral haemorrhagic fevers, the main target cells for replication are those of monocyte, macrophage lineage. The virus causes a haemorrhagic fever with high mortality rates in pigs, but persistently infects its natural hosts, warthogs, bushpigs and soft ticks of the Ornithodoros species with no disease signs. The virus encodes enzymes required for replication and transcription of the genome, including elements of a base excision repair system, structural proteins and many proteins that are not essential for replication in cells but have roles in virus survival and transmission in its hosts. Virus replication takes place in perinuclear factory areas. Assembly of the icosahedral capsid occurs on modified membranes from the endoplasmic reticulum. Products from proteolytically processed polyproteins form the core shell between the internal membrane and the nucleoprotein core. An additional outer membrane is gained as particles bud from the plasma membrane. The virus encodes proteins that inhibit signalling pathways in infected macrophages and thus modulate transcriptional activation of immune response genes. In addition the virus encodes proteins which inhibit apoptosis of infected cells to facilitate production of progeny virions. Viral membrane proteins with similarity to cellular adhesion proteins modulate interaction of virus-infected cells and extracellular virions with host components.
More info: Animal Viruses: Molecular Biology
Featured book: Animal Viruses: Molecular Biology Edited by: Thomas C. Mettenleiter and Francisco Sobrino In this book an international panel of leading virologists provide a state-of-the-art overview of the field, comprehensively detailing the current understanding of viruses, their replication, evolution and interaction with the host. The authors emphasize strategic and methodological aspects of current research, and provide key related references. Topics include foot-and-mouth disease virus, Pestivirus, Arteriviridae, Coronaviruses (including SARS), Herpesviridae, Paramyxoviridae, influenza viruses, Reoviridae, porcine circoviruses, Asfarviridae and much more. An essential text for all virology laboratories.
Bluetongue Virus: Current Research
From: Roy, P. (2008) Structure and Function of Bluetongue Virus and its Proteins. Chapter 4 In: Segmented Double-stranded RNA Viruses. Patton J.T. (Ed.) Caister Academic Press, UK
Bluetongue virus (BTV) is well characterized both genetically (the sequence was completed in 1989) and structurally. Understanding of the molecular biology of the virus and mapping the role of each protein in virus life cycle has benefited significantly through the availability of recombinant BTV proteins and sub-viral particles. In addition the structure of BTV proteins, core and virionparticles have contributed greatly to understanding the mechanism of protein–protein interaction in the virus assembly pathway of BTV and other orbiviruses. Most importantly, information gained from these studies has laid sound foundation for the generation of safe BTV vaccines with the possibility of use in animals in the near future. Latterly, studies have concentrated on the fundamental mechanisms that are used by the virus to invade, replicate in and escape from susceptible host cells. Progress has been made in understanding the structure and entry of intact virus particles, the role of each enzymatic protein in the transcription complex, the critical interactions that occur between the viral non-structural proteins and viral RNA and the role of cellular proteins in non-enveloped virus egress.
Despite these advances, some critical questions remain unanswered for the BTV life cycle and a more complete understanding of the interactions between the virus and the host cell is required for these to be addressed. For example, although progress has been made in the identification of signals for the recruitment of BTV RNA segments into the virion assembly site in the host cell cytoplasm, it has not been possible yet to determine how exactly each genome segment is packaged into the progeny virus. It is also not apparent when and how these genome segments wrap around the polymerase complex once the RNA has been recruited. One of the major drawbacks of research with BTV and other members of Reoviridae has been the lack of availability of a suitable system for genetic manipulation of the virus. This has been a major obstacle in understanding the replication processes of these viruses. However, one of the recent developments in the field of BTV research has been to rescue live virus from transfection of BTV transcripts. There is no doubt that this will be soon extended to establish in vitro manipulative genetic system and will be utilized to address some of these remaining questions.
Very little is known of the intracellular trafficking of newly generated virions although there are some indications of involvement of the cytoskeleton, intermediate filaments and vimentin during BTV morphogenesis. Host–virus interactions during virus trafficking will be one of the future areas needing intense attention. Recent work has revealed unexpected and striking parallels between the entry and release pathways of BTV and pathways involved in entry and release of enveloped viruses. These parallels may be the result of an enveloped ancestor virus or because there are a limited number of cellular pathways that can be useful for the egress of large protein complexes from cells. It is notable that the NS3 glycoprotein of BTV is an integral membrane protein that is functionally involved in virus egress by bridging between the outer capsid protein VP2 and the cellular export machinery. Although no cell-free enveloped form of BTV has been isolated, budding of BTV particles from infected cells at the plasma membrane are quite apparent. The exact role of NS3 in this process and the role of host proteins (Annexin II and p11, Tsg101 and MVB) and their contribution in the release of non-enveloped viruses, such as BTV, remains to be clarified.
More information Bluetongue Virus (Protein Structure and Molecular Biology)
Bluetongue virus (BTV) is well characterized both genetically (the sequence was completed in 1989) and structurally. Understanding of the molecular biology of the virus and mapping the role of each protein in virus life cycle has benefited significantly through the availability of recombinant BTV proteins and sub-viral particles. In addition the structure of BTV proteins, core and virionparticles have contributed greatly to understanding the mechanism of protein–protein interaction in the virus assembly pathway of BTV and other orbiviruses. Most importantly, information gained from these studies has laid sound foundation for the generation of safe BTV vaccines with the possibility of use in animals in the near future. Latterly, studies have concentrated on the fundamental mechanisms that are used by the virus to invade, replicate in and escape from susceptible host cells. Progress has been made in understanding the structure and entry of intact virus particles, the role of each enzymatic protein in the transcription complex, the critical interactions that occur between the viral non-structural proteins and viral RNA and the role of cellular proteins in non-enveloped virus egress.
Despite these advances, some critical questions remain unanswered for the BTV life cycle and a more complete understanding of the interactions between the virus and the host cell is required for these to be addressed. For example, although progress has been made in the identification of signals for the recruitment of BTV RNA segments into the virion assembly site in the host cell cytoplasm, it has not been possible yet to determine how exactly each genome segment is packaged into the progeny virus. It is also not apparent when and how these genome segments wrap around the polymerase complex once the RNA has been recruited. One of the major drawbacks of research with BTV and other members of Reoviridae has been the lack of availability of a suitable system for genetic manipulation of the virus. This has been a major obstacle in understanding the replication processes of these viruses. However, one of the recent developments in the field of BTV research has been to rescue live virus from transfection of BTV transcripts. There is no doubt that this will be soon extended to establish in vitro manipulative genetic system and will be utilized to address some of these remaining questions.
Very little is known of the intracellular trafficking of newly generated virions although there are some indications of involvement of the cytoskeleton, intermediate filaments and vimentin during BTV morphogenesis. Host–virus interactions during virus trafficking will be one of the future areas needing intense attention. Recent work has revealed unexpected and striking parallels between the entry and release pathways of BTV and pathways involved in entry and release of enveloped viruses. These parallels may be the result of an enveloped ancestor virus or because there are a limited number of cellular pathways that can be useful for the egress of large protein complexes from cells. It is notable that the NS3 glycoprotein of BTV is an integral membrane protein that is functionally involved in virus egress by bridging between the outer capsid protein VP2 and the cellular export machinery. Although no cell-free enveloped form of BTV has been isolated, budding of BTV particles from infected cells at the plasma membrane are quite apparent. The exact role of NS3 in this process and the role of host proteins (Annexin II and p11, Tsg101 and MVB) and their contribution in the release of non-enveloped viruses, such as BTV, remains to be clarified.
More information Bluetongue Virus (Protein Structure and Molecular Biology)