PMID- 15858001 OWN - NLM STAT- MEDLINE DCOM- 20050620 LR - 20240510 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 79 IP - 10 DP - 2005 May TI - 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. PG - 6162-71 AB - 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. FAU - Peng, Weiping AU - Peng W AD - Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, Fair Street at East Campus Loop, Lincoln, NE 68583-0905, USA. FAU - Henderson, Gail AU - Henderson G FAU - Inman, Melissa AU - Inman M FAU - BenMohamed, Lbachir AU - BenMohamed L FAU - Perng, Guey-Chuen AU - Perng GC FAU - Wechsler, Steven L AU - Wechsler SL FAU - Jones, Clinton AU - Jones C LA - eng GR - 1P20RR15635/RR/NCRR NIH HHS/United States GR - R01 EY012823/EY/NEI NIH HHS/United States GR - R01 EY013191/EY/NEI NIH HHS/United States GR - EY13701/EY/NEI NIH HHS/United States GR - EY13191/EY/NEI NIH HHS/United States GR - EY12823/EY/NEI NIH HHS/United States GR - P20 RR015635/RR/NCRR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Interferon-alpha) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (Viral Proteins) RN - 0 (latency associated transcript, herpes simplex virus-1) RN - 77238-31-4 (Interferon-beta) SB - IM MH - Animals MH - Disease Models, Animal MH - Female MH - Herpes Simplex/*immunology MH - Herpesvirus 1, Human/genetics/*immunology MH - Humans MH - Interferon-alpha/*biosynthesis/genetics MH - Interferon-beta/*biosynthesis/genetics MH - Mice MH - MicroRNAs MH - Neuroblastoma/immunology/virology MH - RNA, Messenger/analysis MH - Time Factors MH - Trigeminal Ganglion/immunology/*virology MH - Viral Proteins/*immunology PMC - PMC1091686 EDAT- 2005/04/29 09:00 MHDA- 2005/06/21 09:00 PMCR- 2005/05/01 CRDT- 2005/04/29 09:00 PHST- 2005/04/29 09:00 [pubmed] PHST- 2005/06/21 09:00 [medline] PHST- 2005/04/29 09:00 [entrez] PHST- 2005/05/01 00:00 [pmc-release] AID - 79/10/6162 [pii] AID - 1972-04 [pii] AID - 10.1128/JVI.79.10.6162-6171.2005 [doi] PST - ppublish SO - J Virol. 2005 May;79(10):6162-71. doi: 10.1128/JVI.79.10.6162-6171.2005.