The polyserine tract of herpes simplex virus ICP4 is required for normal viral gene expression and growth in murine trigeminal ganglia

被引:23
作者
Bates, PA [1 ]
DeLuca, NA [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA
关键词
D O I
10.1128/JVI.72.9.7115-7124.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
ICP4 of herpes simplex virus (HSV) is essential for productive infection due to its central role in the regulation of HSV transcription. This study identified a region of ICP4 that is not required for viral growth in culture or at the periphery of experimentally inoculated mice but is critical for productive growth in the trigeminal ganglia. This region of ICP4 encompasses amino acids 184 to 198 and contains 13 nearly contiguous serine residues that are highly conserved among the alphaherpesviruses. A mutant in which this region is deleted (Delta SER) was able to grow on the corneas of mice and be transported back to the trigeminal ganglia. Delta SER did not grow in the trigeminal ganglia but did express low levels of several immediate-early (ICP4 and ICP27) and early (thymidine kinase [tk] and UL42) genes. It expressed very low levels of the late gC gene and did not appear to replicate DNA. This pattern of gene expression was similar to that observed for a tk mutant, dlsptk. Both Delta SER and dlsptk expressed higher levels of the latency-associated transcript (LAT) per genome earlier in infected ganglia than did the wild-type virus, KOS. However, infected ganglia from all three viruses accumulated the same level of LAT per genome at 30 days postinfection (during latency). The data suggest that the polyserine tract of ICP4 provides an activity that is required for lytic infection in ganglia to progress to viral DNA synthesis and full lytic gene expression. In the absence of this activity, higher levels of LAT per genome accumulate earlier in infection than with wild-type virus.
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页码:7115 / 7124
页数:10
相关论文
共 78 条
[1]   COMPLETE NUCLEOTIDE-SEQUENCE OF THE MAREKS-DISEASE VIRUS-ICP4 GENE [J].
ANDERSON, AS ;
FRANCESCONI, A ;
MORGAN, RW .
VIROLOGY, 1992, 189 (02) :657-667
[2]   TRANSCRIPTIONAL ANALYSIS OF THE REGION OF THE HERPES-SIMPLEX VIRUS TYPE-1 GENOME CONTAINING THE UL8, UL9, AND UL10 GENES AND IDENTIFICATION OF A NOVEL DELAYED-EARLY GENE-PRODUCT, OBPC [J].
BARADARAN, K ;
DABROWSKI, CE ;
SCHAFFER, PA .
JOURNAL OF VIROLOGY, 1994, 68 (07) :4251-4261
[3]   REGULATION AND CELL-TYPE-SPECIFIC ACTIVITY OF A PROMOTER LOCATED UPSTREAM OF THE LATENCY-ASSOCIATED TRANSCRIPT OF HERPES-SIMPLEX VIRUS TYPE-1 [J].
BATCHELOR, AH ;
OHARE, P .
JOURNAL OF VIROLOGY, 1990, 64 (07) :3269-3279
[4]   LOCALIZATION OF CIS-ACTING SEQUENCE REQUIREMENTS IN THE PROMOTER OF THE LATENCY-ASSOCIATED TRANSCRIPT OF HERPES-SIMPLEX VIRUS TYPE-1 REQUIRED FOR CELL-TYPE-SPECIFIC ACTIVITY [J].
BATCHELOR, AH ;
OHARE, P .
JOURNAL OF VIROLOGY, 1992, 66 (06) :3573-3582
[5]   IDENTIFICATION OF A PROMOTER MAPPING WITHIN THE REITERATED SEQUENCES THAT FLANK THE HERPES-SIMPLEX VIRUS TYPE-1 UL REGION [J].
BOHENZKY, RA ;
PAPAVASSILIOU, AG ;
GELMAN, IH ;
SILVERSTEIN, S .
JOURNAL OF VIROLOGY, 1993, 67 (02) :632-642
[6]  
Carrozza MJ, 1996, MOL CELL BIOL, V16, P3085
[7]   A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus [J].
Chen, SH ;
Kramer, MF ;
Schaffer, PA ;
Coen, DM .
JOURNAL OF VIROLOGY, 1997, 71 (08) :5878-5884
[8]   DNA NUCLEOTIDE-SEQUENCE ANALYSIS OF THE IMMEDIATE-EARLY GENE OF PSEUDORABIES VIRUS [J].
CHEUNG, AK .
NUCLEIC ACIDS RESEARCH, 1989, 17 (12) :4637-4646
[9]   MAPPING OF HERPES-SIMPLEX VIRUS-1 NEUROVIRULENCE TO GAMMA-134.5, A GENE NONESSENTIAL FOR GROWTH IN CULTURE [J].
CHOU, J ;
KERN, ER ;
WHITLEY, RJ ;
ROIZMAN, B .
SCIENCE, 1990, 250 (4985) :1262-1266
[10]   THYMIDINE KINASE-NEGATIVE HERPES-SIMPLEX VIRUS MUTANTS ESTABLISH LATENCY IN MOUSE TRIGEMINAL GANGLIA BUT DO NOT REACTIVATE [J].
COEN, DM ;
KOSZVNENCHAK, M ;
JACOBSON, JG ;
LEIB, DA ;
BOGARD, CL ;
SCHAFFER, PA ;
TYLER, KL ;
KNIPE, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (12) :4736-4740