The locus encompassing the latency-associated transcript of herpes simplex virus type 1 interferes with and delays interferon expression in productively infected neuroblastoma cells and trigeminal ganglia of acutely infected mice

被引:44
作者
Peng, WP
Henderson, G
Inman, M
BenMohamed, L
Perng, GC
Wechsler, SL
Jones, C
机构
[1] Univ Nebraska, Nebraska Ctr Virol, Dept Vet & Biomed Sci, Lincoln, NE 68583 USA
[2] Univ Calif Irvine, Sch Med, Dept Ophthalmol, Irvine, CA 92697 USA
关键词
D O I
10.1128/JVI.79.10.6162-6171.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is the only abundant viral transcript expressed in latently infected neurons. LAT inhibits apoptosis, suggesting that it regulates latency by promoting the survival of infected neurons. The LAT locus also contains a newly described gene (AL), which is antisense to LAT and partially overlaps LAT encoding sequences. When human (SK-N-SH) or mouse (neuro-2A) neuroblastoma cells were infected with a virus that does not express LAT or AL gene products (dLAT2903), beta interferon (IFN-beta) and IFN-alpha RNA expression was detected earlier relative to the same cells infected with HSV-1 strains that express LAT and AL. Infection of neuro-2A cells with dLAT2903 also led to higher levels of IFN-beta promoter activity than in cells infected with wild-type (wt) HSV-1. In contrast, IFN RNA expression was the same when human lung fibroblasts were infected with dLAT2903 or wt HSV-1. When BALB/c mice were infected with dLAT2903, IFN-alpha and IFN-beta RNA expression was readily detected in trigeminal ganglia (TG) 4 days after infection. These transcripts were not detected in TG of mice infected with wt HSV-1 or dLAT2903R (marker-rescued dLAT2903) until 6 days postinfection. When TG single-cell suspensions from infected BALB/c mice were prepared and incubated in vitro with wt HSV-1 as a source of antigen, TG cultures prepared from mice infected with dLAT2903 produced and secreted higher levels of IFN protein than wt HSV-1 or dLAT2903R. Collectively, these studies suggest that the LAT locus interferes with and delays IFN expression.
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页码:6162 / 6171
页数:10
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