Alphaherpesvirus
Molecular Chaperones and Alphaherpesvirus Infection
Category: Virology
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
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
HSV-1 Latency LATs
Category: Virology
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
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
HSV-1 and the DNA Damage Response
Category: Virology
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
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
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