HSV-1 infection
Intrinsic Resistance to HSV-1 Infection
Category: Virology
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
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
HSV-1 ICP27
Category: Virology | Regulation
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
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