期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：1
页码：E49-E55
DOI：10.1073/pnas.1422657112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe mechanism by which HSV enters into a silent, latent state in neurons remains a major problem in virology. The only manifestations of viral gene expression during latency are the accumulation of a noncoding transcript and a set of microRNAs (miRNAs). Available data support the hypothesis that these play a role in the maintenance of the latent state and predict the accumulation of a different set of miRNAs during latency and reactivation. This report (i) supports the hypothesis that miRNAs arise during latency from multiple transcriptional events on the basis of location and differences in transcriptional regulation in productively infected cells and (ii) specifically identifies miRNAs that arise during reactivation and that differ from those accumulating in productively infected cells. The key events in herpes simplex virus (HSV) infections are (i) replication at a portal of entry into the body modeled by infection of cultured cells; (ii) establishment of a latent state characterized by a sole latency-associated transcript and microRNAs (miRNAs) modeled in murine peripheral ganglia 30 d after inoculation; and (iii) reactivation from the latent state modeled by excision and incubation of ganglia in medium containing anti-NGF antibody for a timespan of a single viral replicative cycle. In this report, we examine the pattern of synthesis and accumulation of 18 HSV-1 miRNAs in the three models. We report the following: (i) H2-3P, H3-3P, H4-3P, H5-3P, H6-3P, and H7-5P accumulated in ganglia harboring latent virus. All but H4-3P were readily detected in productively infected cells, and most likely they originate from three transcriptional units. (ii) H8-5P, H15, H17, H18, H26, and H27 accumulated during reactivation. Of this group, only H26 and H27 could be detected in productively infected cells. (iii) Of the 18 we have examined, only 10 miRNAs were found to accumulate above background levels in productively infected cells. The disparity in the accumulation of miRNAs in cell culture and during reactivation may reflect differences in the patterns of regulation of viral gene expression during productive infection and during reactivation from the latent state.
