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
HSV-1 DNA Replication
Category: Virology
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
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