HSV1 Latency Sites after Inoculation in the Lip: Assessment of their Localization and Connections to the Eye

Labétoulle, Marc; Maillet, Séverine; Efstathiou, Stacey; Dezélée, Sybille; Frau, E; Lafay, Florence

doi:10.1167/iovs.02-0464

Cited by 37 publications

(40 citation statements)

References 56 publications

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“…These results are in agreement with the observation that HSV-1 latency in humans occurs within the TG, the central, and the autonomic nervous pathways, including the SCG (21,21,23,45,82). However, we observed larger numbers of neurons expressing LATs in the TG than in the other latently infected structures despite a similar level of productive infection (39). These data suggested that fundamentally different patterns of HSV-1 latency may occur in distinct neuronal cell types.…”

supporting

confidence: 92%

“…Wild-type HSV-1 strain SC16 (30) and the recombinant strain SC16 110LacZ (41), which contains an ICP0 promoter-driven lacZ inserted into the nonessential US5 gene of HSV-1, were used. Viruses were propagated and titrated as previously described (37)(38)(39).…”

Section: Methodsmentioning

confidence: 99%

“…A 1-l suspension of SC16 or SC16 110LacZ containing 10 6 plaque-forming units was inoculated into the left upper lip of the mice, and the mice were observed daily for clinical signs of ocular infection from days 0 to 28 postinoculation (dpi), as previously described (37,39). Mice that showed clinical signs of ocular disease such as blepharitis, conjunctivitis, keratitis, or iritis (about 70% of the mice) between 6 and 10 dpi were randomly sacrificed at either 6 dpi for the acute infection study or 28 dpi, when clinical signs were resolved, for the latent infection study.…”

Section: Methodsmentioning

confidence: 99%

“…(39, 40) (i) A digoxigenin-labeled riboprobe was produced from EcoRI digestion of the pSLAT5 plasmid, provided by Jane Arthur (2), and was in vitro transcribed with T3 RNA polymerase, using the RNA Dig transcription kit, (Roche, Meylan, France). (ii) The riboprobe (100 ng) was hybridized on tissue sections overnight at 64°C (39). A stringent wash in 0.1ϫ SSC (15 mM Na, 1.5 mM sodium citrate) plus 30% deionized formamide and 10 mM Tris-HCL (pH 7.5) was carried out at 64°C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Since most data concerning LAT and ICP0 gene expression during HSV-1 latency is derived from the analysis of sensory neurons, especially those of TG, we used the oro-ocular model of HSV-1 infection (37,39), which allowed comparison of LAT and ICP0 transcription in various types of latently infected neurons.…”

mentioning

confidence: 99%

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Herpes Simplex Virus Type 1 Latently Infected Neurons Differentially Express Latency-Associated and ICP0 Transcripts

Maillet

Naas

Crépin

et al. 2006

J Virol

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Herpes simplex virus type 1 (HSV-1) is a human neurotropic virus, which establishes lifelong latent infection. During the acute phase of infection, viral replication is characterized by the expression of immediate early (IE), early, and late genes in an ordered cascade that leads to the release of infectious particles that can attach to nerve endings. Following axonal transport to neuronal cell bodies, HSV-1 can either replicate or persist in a latent state in the infected host (62).During latency infectious virus cannot be detected in neuronal tissues (62). The viral genome is circularized, complexed with histones, and maintained in a repressed state with the exception of the latency-associated transcripts (LATs) that are encoded within the repeats flanking the unique long region of the HSV-1 genome (12, 33, 60). The LATs (2 kb and 1.5 kb in size) are stable unpolyadenylated introns that are retained within the nuclei of latently infected neurons (reviewed in references 33 and 56) and are spliced from a primary 8.3-kb transcript (19). Their unusual stability has been related to modifications in the consensus sequences of splicing (84), resulting in an unstable 6.3-kb spliced exon (13, 85) and a stable 2-kb LAT intron that is expressed during both acute and latent infections (73,84). During latent neuronal infection, the 2-kb LAT may undergo subsequent splicing that results in a 1.5-kb LAT (1,46,70). The functions of LATs are not yet clearly understood, but mutational analyses and transfection assays of LATs strongly suggest that they have a key role in establishment of latency and/or viral reactivation (29,31,53,64,71,77), besides their antiapoptotic, anti-interferon, and proneuronal survival properties (24,32,52,54,55,78).Several studies failed to detect lytic viral gene expression during HSV-1 latency (20,33). However, some studies reported the detection of transcripts from genes encoding the immediate-early viral protein ICP4 and the early viral protein thymidine kinase (TK) in latently infected trigeminal ganglion (TG) neurons (9, 34). This observation was initially interpreted as a possible result of spontaneous reactivation (33). Since the gene encoding the ICP0 protein of HSV-1 is contained entirely within the region of the HSV-1 genome encoding LATs (reviewed in reference 3), it might be transcribed during latency, as recently reported by Chen et al. for latently infected TG neurons (10). ICP0 is the first viral protein produced during the productive cycle and is thus classically considered a relevant indicator of early-stage reactivation (18,59,65). It nonspecifically transactivates both viral and cellular promoters (18,25,42) and plays a crucial role in the initiation of productive infection following low-multiplicity infections of cells in culture (7,8,17,63). ICP0 is able to initiate both viral gene expression from quiescent genomes in cells in culture and viral reactivation from latently infected sensory neurons in vivo (6, 26, 27,

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confidence: 92%