1887

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Volume 77, Issue 8

Role of -acting sequences of the ICPO promoter of herpes simplex virus type 1 in viral pathogenesis, latency and reactivation Free

Abstract

A mutant herpes simplex virus type 1, termed ΔTfi, with a 350bp deletion of the Sp1, NF-κB, TAATGARATs, C/EBP and F2 DNA-binding elements from -420 to -70 relative to the transcriptional start site of ICPO (Vmw 110), was generated and characterized. The efficiency of plating of ΔTfi was reduced on Vero cells and it expressed correctly initiated ICPO RNA in the presence of cycloheximide, although RNA levels were 2.5-fold lower than with wild-type (KOS) and marker-rescued (ΔTfiR) viruses. This was consistent with a demonstrated reduction in ICPO protein expression for ΔTfi at early times post-infection and a 3-fold reduction in ICPO-dependent transactivation of the ICP6 promoter. KOS, ΔTfi and ΔTfiR replication in murine corneas and trigeminal ganglia were comparable when measured on a complementing cell line, but ΔTfi titres appeared 15- to 50-fold lower when measured on Vero cells. ΔTfi was correspondingly less virulent than wild-type or marker-rescued viruses in both immunocompetent and SCID mice. ΔTfi, however, established and reactivated from latency with efficiencies comparable to wild-type and marker-rescued viruses. These results demonstrate that although this deletion of the ICPO promoter results in lower levels of ICPO and decreased virulence the establishment of and reactivation from latency are unaffected. This indicates that elements which regulate ICPO expression and virulence during acute infection may be distinct from those involved in reactivation.

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© Journal of General Virology 1996
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1996-08-01
2024-04-25
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Role of cis-acting sequences of the ICPO promoter of herpes simplex virus type 1 in viral pathogenesis, latency and reactivation
J. Gen. Virol. 77, 1853 (1996); https://doi.org/10.1099/0022-1317-77-8-1853
/content/journal/jgv/10.1099/0022-1317-77-8-1853
/content/journal/jgv/10.1099/0022-1317-77-8-1853
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