Herpes virus
Immunity to Herpes Simplex Virus
Category: Virology | Immunology
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
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
Strategies Against Herpes Simplex Virus
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
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
Herpes Simplex Virus Entry
Category: Virology
from Roselyn J. Eisenberg, Ekaterina E. Heldwein, Gary H. Cohen and Claude Krummenacher writing in Alphaherpesviruses: Molecular Virology:
Membrane fusion allows exchange of materials between cellular compartments enclosed by lipid membranes. Similarly, entry of enveloped viruses into cells allows the viral contents to be delivered by fusion of the envelope with a target cell membrane. Fusion requires disruption of both layers of the two membranes. For most enveloped viruses, a single surface glycoprotein undergoes conformational changes that bring the bilayer of the virus in proximity with that of the host cell and fusion ensues. In contrast, herpesvirus entry requires three virion glycoproteins, gB and a gH/gL heterodimer, that function as the core fusion machinery. Some herpesviruses require additional proteins, e.g. alphaherpesviruses (with a few exceptions) initiate fusion by binding of glycoprotein gD to a cell receptor. A conformational change then exposes the normally hidden receptor binding residues of gD. This change and/or the exposed residues trigger gB and gH/gL to effect virus-cell and cell-cell fusion. Because of the multiplicity of proteins involved in HSV entry as opposed to entry of enveloped RNA viruses, it has been difficult to unravel the mechanism of how the four entry glycoproteins function. Some favor formation of a multiprotein fusion complex while others suggest it may be more of a stepwise process. Solution of the structures of all four entry proteins, coupled with existing and new information has solved much of this mystery. We now have a much better idea of the outline of the process, but the challenge for the future will be to fill in important details. It is clear that entry of HSV occurs in an exquisitely regulated stepwise process that begins with binding of gD to a receptor, activation of the regulatory protein gH/gL which in turn up-regulates the fusogenic activity of gB. Thus, in some ways, HSV entry is remarkably similar overall to entry by simpler RNA viruses, such as influenza. A single fusion protein gB carries out fusion. What distinguishes HSV entry is the double regulation of this process.
Further reading: Alphaherpesviruses: Molecular Virology
Membrane fusion allows exchange of materials between cellular compartments enclosed by lipid membranes. Similarly, entry of enveloped viruses into cells allows the viral contents to be delivered by fusion of the envelope with a target cell membrane. Fusion requires disruption of both layers of the two membranes. For most enveloped viruses, a single surface glycoprotein undergoes conformational changes that bring the bilayer of the virus in proximity with that of the host cell and fusion ensues. In contrast, herpesvirus entry requires three virion glycoproteins, gB and a gH/gL heterodimer, that function as the core fusion machinery. Some herpesviruses require additional proteins, e.g. alphaherpesviruses (with a few exceptions) initiate fusion by binding of glycoprotein gD to a cell receptor. A conformational change then exposes the normally hidden receptor binding residues of gD. This change and/or the exposed residues trigger gB and gH/gL to effect virus-cell and cell-cell fusion. Because of the multiplicity of proteins involved in HSV entry as opposed to entry of enveloped RNA viruses, it has been difficult to unravel the mechanism of how the four entry glycoproteins function. Some favor formation of a multiprotein fusion complex while others suggest it may be more of a stepwise process. Solution of the structures of all four entry proteins, coupled with existing and new information has solved much of this mystery. We now have a much better idea of the outline of the process, but the challenge for the future will be to fill in important details. It is clear that entry of HSV occurs in an exquisitely regulated stepwise process that begins with binding of gD to a receptor, activation of the regulatory protein gH/gL which in turn up-regulates the fusogenic activity of gB. Thus, in some ways, HSV entry is remarkably similar overall to entry by simpler RNA viruses, such as influenza. A single fusion protein gB carries out fusion. What distinguishes HSV entry is the double regulation of this process.
Further reading: Alphaherpesviruses: Molecular Virology
Herpes Simplex Virus Regulatory Protein ICP4
Category: Virology | Regulation
ICP4 is expressed from the HSV genome very early in infection. It is a large structurally complex nuclear phosphoprotein that is essential for viral growth largely due to its requirement for the transcriptional activation of most HSV early and late genes. It also acts a repressor of transcription under certain circumstances. The HSV genome is transcribed by RNA polII, and ICP4 interacts with components of the RNA polII transcription machinery to carry out is functions in transcription. The interactions that are important for its functions can be genetically defined implicating a modular composition of the ICP4 protein. ICP4 also plays a specific role in virus growth in sympathetic neurons implicating a specific function in pathogenesis. A recent review describes what is known about ICP4 from many genetic, biological and biochemical studies, from many laboratories.
Further reading: Alphaherpesviruses: Molecular Virology
Further reading: Alphaherpesviruses: Molecular Virology
EBV
A new publication on EBV: Epstein-Barr Virus: Latency and Transformation was published recently. In this book, expert EBV virologists comprehensively review this important subject from a genetic, biochemical, immunological, and cell biological perspective. Topics include: latent infections, EBV leader protein, EBNA-1 in viral DNA replication and persistence, EBNA-2 in transcription activation of viral and cellular genes, the nuclear antigen family 3 in regulation of cellular processes, molecular profiles of EBV latently infected cells, latent membrane protein 1 oncoprotein, regulation of latency by LMP2A, role of noncoding RNAs in EBV-induced cell growth and transformation and the regulation of EBV latency by viral lytic proteins. This book is essential reading for all EBV virologists as well as clinical and basic scientists working on oncogenic viruses read more ...
 | Edited by: Erle S. Robertson ISBN: 978-1-904455-62-2 Publisher: Caister Academic Press Publication Date: April 2010 Cover: Hardback read more ... |