EFFECT OF THE TRANSCRIPTION START REGION OF THE HERPES-SIMPLEX VIRUS TYPE-1 LATENCY-ASSOCIATED TRANSCRIPT PROMOTER ON EXPRESSION OF PRODUCTIVELY INFECTED NEURONS IN-VIVO

被引:26
作者
FARRELL, MJ
MARGOLIS, TP
GOMES, WA
FELDMAN, LT
机构
[1] UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024
[2] UNIV CALIF SAN FRANCISCO,MED CTR,DEPT OPHTHALMOL,FRANCIS I PROCTOR FDN,SAN FRANCISCO,CA 94143
关键词
D O I
10.1128/JVI.68.9.5337-5343.1994
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
It has been previously reported that the latency-associated transcript (LAT) promoter contains a DNA sequence at the LAT transcription start site which resembles the ICP4 consensus DNA binding site and that this site allows ICP4-mediated downregulation of the LAT promoter in transient assays (A. H. Batchelor and P. O'Hare, J. Virol. 64:3269-3279, 1990). We have confirmed these data by showing that an ICP4-expressing plasmid will downregulate lacZ expression from a plasmid containing the LAT promoter and transcription start site (pJA1) and does not downregulate lacZ expression from a plasmid in which the start site has been mutagenized (pWAG15). To determine the role of the LAT transcription start site in regulating LAT promoter activity in the context of the virus, two recombinant viruses, KOS-1 and KOS-15, were studied. KOS-I contains an 863-bp portion of the LAT promoter, including the LAT cap site, fused to the lacZ gene and inserted into the gC locus (T. P. Margolis, F. Sedarati, A. T. Dobson, L. T. Feldman, and J. G. Stevens, Virology 189:150-160, 1992). The second virus (KOS-15) was constructed in identical fashion, using plasmid pWAG-15, which is not downregulated by ICP4. Vero cells productively infected with KOS-15 produce 10-fold more P-galactosidase than do those infected with KOS-1. In murine dorsal root ganglia acutely infected with KOS-1, only 1.2% of dorsal root ganglion neurons that expressed viral antigen also expressed beta-galactosidase. In contrast, in KOS-15-infected mice, beta-galactosidase was detected in 18% of viral antigen-positive neurons. Similar findings were observed in trigeminal ganglia acutely infected with KOS-1 and KOS-15. Thus, the region encompassing the LAT transcription start site appears to play an important role in repression of the LAT promoter activity not only in vitro but also in acutely infected neurons in vivo. These results suggest that during productive infection with HSV-1, LAT expression is tightly regulated.
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页码:5337 / 5343
页数:7
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