Herpes simplex virus latency

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are ubiquitous human pathogens. They share with other herpesviruses the ability to establish lifelong latent infection of the host. Periodic reactivation from latency is responsible for most of the clinical disease burden of HSV infection. This review focuses on what we have learned from molecular studies in model systems of HSV latency, and the implications these findings have for treating recurrent HSV disease.     

Herpes simplex virus (HSV)

Herpes simplex virus (HSV), the prototype of the herpesvirus family, causes a variety of diseases in human. In this review, I focus on the molecular mechanism of HSV infection including recent advance on this research field.     

Herpes simplex virus latency and the immune response

Following infection, herpes simplex virus establishes latency in the nervous system and recurrences of lytic replication occur periodically. Molecular events which may determine how virus enters latency, how it is maintained and what occurs during reactivation have been investigated. The role of the immune response in limiting infection of the nervous system, influencing the latent state and removing virus from peripheral sites following reactivation has also been studied.     

Herpes simplex virus eliminates host mitochondrial DNA

Mitochondria have crucial roles in the life and death of mammalian cells, and help to orchestrate host antiviral defences. Here, we show that the ubiquitous human pathogen herpes simplex virus (HSV) induces rapid and complete degradation of host mitochondrial DNA during productive infection of cultured mammalian cells. The depletion of mitochondrial DNA requires the viral UL12 gene, which encodes a conserved nuclease with orthologues in all herpesviruses. We show that an amino-terminally truncated UL12 isoform-UL12.5-localizes to mitochondria and triggers mitochondrial DNA depletion in the absence of other HSV gene products. By contrast, full-length UL12, a nuclear protein, has little or no effect on mitochondrial DNA levels. Our data document that HSV inflicts massive genetic damage to a crucial host organelle and show a novel mechanism of virus-induced shutoff of host functions, which is likely to contribute to the cell death and tissue damage caused by this widespread human pathogen.