Alternative splicing of the latency-related transcript of bovine herpesvirus 1 yields RNAs containing unique open reading frames

The latency-related transcript (LRT) of bovine herpesvirus 1 (BHV-1) is the only abundant viral RNA detected during latency. A previous study (A. Hossain, L. M. Schang, and C. Jones, J. Virol, 69:5345-5352, 1995) concluded that splicing of polyadenylated [poly(A)(+)] and splicing of nonpolyadenylated [poly(A)(-)] LRT are different. In this study, splice junction sites of LRT were identified. In trigeminal ganglia of acutely infected calves (1, 7, or 15 days postinfection [p.i.]) or in latently infected calves (60 days p.i.), alternative splicing of poly(A)(+) LRT occurred. Productive viral gene expression in trigeminal ganglia is readily detected from 2 to 7 days p.i. but not at 15 days p.i. (L. M. Schang and C. Jones, J. Virol, 71:6786-6795, 1997), suggesting that certain aspects of a lytic infection occur in neurons and that these factors influence LRT splicing. Splicing of poly(A)(-) LRT was also detected in transfected COS-7 cells or infected MDBK cells, DNA sequence analysis of spliced LRT cDNAs, poly(A)(+) or poly(A)(-), revealed nonconsensus splice signals at exon/intron and intron/exon boundaries. The GC-AG splicing signal utilized by the herpes simplex virus type 1 latency-associated transcript in latently infected mice is also used by LRT in latently infected calves, Taken together, these results led us to hypothesize that (i) poly(A)(+) LRT is spliced in trigeminal ganglia by neuron-specific factors, (ii) viral or virus-induced factors participate in splicing, and (iii) alternative splicing of LRT may result in protein isoforms which have novel biological properties.