The outcome of herpes simplex virus type 1 (HSV-1) infection depends upon the interplay of both host and viral factors. Earlier studies have shown that ORF P is repressed by infected cell protein 4 (ICP4), the major viral regulatory protein, binding to its cognate site at the transcription initiation site of ORF P. Infection with herpes simplex virus 1 (HSV-1) is usually associated with cold sores of the lips, mouth and face. We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of Beta-amyloid (ABeta), so that less of the viral DNA is seen to be associated with ABeta in the brain. These and earlier results indicate that ORF P and ORF O together have the capacity to reduce the synthesis or block the expression of regulatory proteins essential for viral replication in productive infection. The herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) cause two kinds of infections. At least seven viral genes encode proteins (UL6, UL15, UL17, UL25, UL28, UL32, and UL33) that are required for DNA cleavage and packaging of herpes simplex virus type 1 (HSV-1) DNA.
Tn5 insertional mutagenesis of the ICP4 regulatory gene determined that down-regulation of LAP2 required the ICP4 transactivating domain and targeted the minimal promoter region as the site of action by ICP4. Replicating recombinant viruses containing a LAP2-lacZ reporter gene cassette in an ectopic site (glycoprotein C locus) were shown to be active in mouse trigeminal ganglia. Taken together, these experiments suggest that the LAT region of the HSV-1 genome contains at least two latency-active promoters which may play different roles in expressing the various LATs. Alternatively, these promoters may comprise a larger promoter-regulatory complex which may influence transcription during latency.