Induction of apoptosis accelerates reactivation of latent HSV-1 in ganglionic organ cultures and replication in cell cultures.
Herpes simplex viruses replicate at the portal of entry into the body and are transported retrograde to sensory neurons in which they can establish a silent, latent infection characterized by the expression of a noncoding latency-associated transcript and a set of microRNAs. At the portal of entry into the body and in cell culture a viral protein, VP16, recruits cellular proteins that initiate a sequential derepression of several kinetic classes of viral genes. Earlier studies have shown that upon reactivation of latent virus in ganglionic organ cultures all genes are derepressed at once, thus obviating the need for VP16 to initiate sequential derepression of viral genes. One hypothesis that could explain the data is that the massive reactivation of all classes of viral genes is the consequence of activation of an apoptotic pathway. Here we show that two proapoptotic drugs, dexamethasone and 2[[3-(2,3-dichlorophenoxy)propyl]amino]-ethanol, each accelerates viral gene expression in ganglionic organ cultures. We also show that in cultured cells apoptosis induced by dexamethasone accelerates viral gene expression and accumulation of infectious virus. The results are surprising in light of the relatively large number of viral proteins that independently block apoptosis induced by viral gene products or exogenous agents. The results suggest that the virus may rely on apoptosis to exit from latency but that apoptosis may be detrimental for virus replication or spread at the portal of entry into the body.
Marjorie B Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
Te
T
Du
Guoying
G
Zhou
Bernard
B
Roizman
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002522:Chlorocebus aethiops; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000166:cytology / Q000821:virology*; D014709:Vero Cells; D014775:Virus Activation / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
D003907:Dexamethasone