Lytic Gene Expression Is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response

PLoS Pathogens

Francis R. Carbone¹  David C. Tscharke²  Joel Z. Ma²  Tiffany A. Russell³  Tim Spelman⁴ 

[1] Centre of Population Health, Burnet Institute, Melbourne, Victoria, Australia;Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia;Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Canberra, Australian Capital Territory, Australia;Victorian Infectious Diseases Service, Melbourne Health, Melbourne, Victoria, Australia

关键词: Neurons;    Gene expression;    Viral persistence;    latency;    DNA transcription;    Herpes simplex virus;    Virus effects on host gene expression;    Viral replication;    Viral gene expression;   

DOI  :  10.1371/journal.ppat.1004237

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Herpes simplex viruses (HSV) are significant human pathogens that provide one of the best-described examples of viral latency and reactivation. HSV latency occurs in sensory neurons, being characterized by the absence of virus replication and only fragmentary evidence of protein production. In mouse models, HSV latency is especially stable but the detection of some lytic gene transcription and the ongoing presence of activated immune cells in latent ganglia have been used to suggest that this state is not entirely quiescent. Alternatively, these findings can be interpreted as signs of a low, but constant level of abortive reactivation punctuating otherwise silent latency. Using single cell analysis of transcription in mouse dorsal root ganglia, we reveal that HSV-1 latency is highly dynamic in the majority of neurons. Specifically, transcription from areas of the HSV genome associated with at least one viral lytic gene occurs in nearly two thirds of latently-infected neurons and more than half of these have RNA from more than one lytic gene locus. Further, bioinformatics analyses of host transcription showed that progressive appearance of these lytic transcripts correlated with alterations in expression of cellular genes. These data show for the first time that transcription consistent with lytic gene expression is a frequent event, taking place in the majority of HSV latently-infected neurons. Furthermore, this transcription is of biological significance in that it influences host gene expression. We suggest that the maintenance of HSV latency involves an active host response to frequent viral activity.

【 授权许可】

CC BY