Herpes simplex virus 1 (HSV-1) and HSV-2 establish latency in different neuronal subtypes (A5؉ and KH10؉) in murine trigeminal ganglia, results which correlate with restricted productive infection in these neurons in vitro. HSV-2 latency-associated transcript (LAT) contains a cis-acting regulatory element near the transcription start site that promotes productive infection in A5؉ neurons and a second element in exon 1 that inhibits productive infection in KH10؉ neurons. HSV-1 contains no such regulatory sequences, demonstrating different mechanisms for regulating productive HSV infection in neurons.
Herpes simplex virus 1 (HSV-1) and HSV-2 express productive cycle genes in some neurons and establish latent infection in others. We previously demonstrated that HSV-1 and HSV-2 preferentially establish latency in different neuronal subtypes in murine sensory ganglia: HSV-1 in A5ϩ neurons and HSV-2 in KH10ϩ neurons (1, 2). In dissociated adult murine trigeminal cultures (AMTC), we previously found that HSV-1 productively infected KH10ϩ but not A5ϩ neurons while HSV-2 productively infected A5ϩ but not KH10ϩ neurons (Fig. 1A) (3). Thus, the neuronal subtypes that restrict productive HSV infection in vitro are the same neurons that harbor latent infection in vivo. Both host and viral factors may play roles in regulating neuronal specificity (1, 2, 4-7). To determine if the latency-associated transcript (LAT) region regulates productive infection in A5ϩ and KH10ϩ neurons, we assayed HSV infection of AMTC using a series of LAT deletion and chimeric viruses (5).The HSV-2 LAT region contains two regulatory sequences for productive infection of neurons. HSV-2 (333) productively infects 36% of A5ϩ neurons in AMTC but only 3% of KH10ϩ neurons (Fig. 1B). In contrast, dLAT (NotI-NotI deletion of the HSV-2 LAT promoter) (Fig. 1D) (8) productively infects only 5% of A5ϩ neurons (Fig. 1B). The LAP2 virus (LAT promoter 2 deletion in HSV-2 exon 1) (Fig. 1D) (9) productively infects A5ϩ and KH10ϩ neurons equivalently (39% and 36%, respectively) (Fig. 1B). Thus, two distinct functional elements within HSV-2 LAT regulate productive infection: the NotI-NotI region promotes productive infection in A5ϩ neurons, and the LAP2 region inhibits productive infection in KH10ϩ neurons.HSV-2/LAT1 is a chimera in which 2.8 kb of the HSV-2 LAT region (promoter, exon 1, and ϳ1.5 kb of the intron, excluding ICP0 coding sequences) was replaced by the same region from HSV-1 (10). HSV-2/LAT1 preferentially establishes latency in A5ϩ neurons in vivo, suggesting that HSV-1 LAT in the context of HSV-2 changes the viral phenotype to that of HSV-1 (1). In AMTC, HSV-2/LAT1 productively infects 22% of KH10ϩ neurons but only 4% of A5ϩ neurons, in contrast to HSV-2 or the rescuant, HSV-2/LAT1-R (Fig. 1C). Thus, the pattern of productive infection with HSV-2/LAT1 resembles that of HSV-1, with productive infection in KH10ϩ neurons but restricted infection in A5ϩ neurons. Since the HSV-1 LAT region in HSV-2/LAT1 replaces sequences that were deleted in dLAT and LAP2, ...
Student-generated weekly learning goals on a neurology clerkship appear to be an effective method to operationalize SRL. For most students, the frequency of the goals allowed for close self-monitoring, and the act of sharing goals with the team opened a new avenue for dialogue between students and their supervisors.
for the European Glaucoma Prevention Study and the Ocular Hypertension Treatment Study IMPORTANCE The contribution of long-term intraocular pressure (IOP) variability to the development of primary open-angle glaucoma is still controversial. OBJECTIVE To assess whether long-term IOP variability data improve a prediction model for the development of primary open-angle glaucoma (POAG) in individuals with untreated ocular hypertension. DESIGN, SETTING, AND PARTICIPANTS This post hoc secondary analysis of 2 randomized clinical trials included data from 709 of 819 participants in the observation group of the Ocular
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