HERPES-SIMPLEX VIRUS TYPE-1 LATENCY-ASSOCIATED TRANSCRIPT (LAT) PROMOTER DELETION MUTANTS CAN EXPRESS A 2-KILOBASE TRANSCRIPT MAPPING TO THE LAT REGION

The results of studies in several laboratories suggest that a TATA box -containing promoter located in the herpes simplex virus type 1 intern al long repeat and long terminal repeat elements drives expression of the latency-associated transcripts (LATs). In the present study, we sh ow that expression of a 2-kb LAT-related transcript can occur in the a bsence of this LAT TATA promoter, indicating the existence of a crypti c promoter. By Northern (RNA) blot analysis, we have examined LAT expr ession by herpes simplex virus type 1 variant strains KOS/29 and 1704, which contain deletions of the LAT promoter region. Our data indicate that KOS/29, despite lacking the 203-bp fragment which contains the L AT TATA box, can express a 2-kb LAT-related transcript during producti ve infection in tissue culture and in mouse trigeminal ganglia during acute infection and reactivation. Similarly, strain 1704, which contai ns a larger deletion in this promoter region, also expresses a 2-kb LA T-related transcript during tissue culture infection and reactivation of latently infected trigeminal ganglia. However, LATs are not express ed with either virus during latency. Northern blot analysis with a sin gle-stranded, oligonucleotide probe demonstrates that the 2-kb LAT and LAT-related transcript are colinear and share a large area of sequenc e similarity. These findings suggest the existence of a second promote r in the LAT gene which can function during lytic infection and reacti vation, at least in the absence of the LAT TATA promoter. We propose t hat this cryptic promoter is located either in a proximal region appro ximately 300 bp upstream of the start site of the 2-kb LAT or in a dis tal region starting over 1,226 bp upstream of this site.