Divergent molecular pathways of productive and latent infection with a virulent strain of herpes simplex virus type 1.
Mutants of herpes simplex virus (HSV) have been used to show that a variety of key genes associated with initiation of lytic infection or replication of viral DNA are not essential for establishment of latency. These observations are extended in the present study, in which a virulent strain of HSV type 1 that is not compromised in its ability to productively infect neurons under favorable conditions was used to demonstrate early divergence of molecular pathways leading to productive and latent infection. Our experimental strategy made unique use of the segmental innervation of the vertebrate trunk to study the spread of virus throughout the peripheral nervous system after inoculation of mouse flanks. Evidence of viral gene expression, including that of immediate-early genes, was transient, confined to ganglia directly innervating the inoculated skin (8th through 12th thoracic segments), and seen only at sites from which infectious virus could be recovered. In contrast, neurons containing latency-associated transcripts and reactivatable virus were more widely distributed (sixth thoracic through first lumbar segments), from which we conclude that replication-competent HSV type 1 can establish latency without initiating productive infection.
Speck
P G
PG
Division of Medical Virology, Institute of Medical and Veterinary Science, Adelaide, Australia.
Simmons
A
A
D000208:Acute Disease; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D004261:DNA Replication; D004268:DNA-Binding Proteins; D005260:Female; D005727:Ganglia, Spinal / Q000382:microbiology*; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000382:microbiology*; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000382:microbiology; D018139:Simplexvirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000032:analysis / Q000235:genetics; D014774:Virulence; D014779:Virus Replication
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1