Efficient Nuclear Export of Herpes Simplex Virus 1 Transcripts Requires both RNA Binding by ICP27 and ICP27 Interaction with TAP/NXF1

Herpes simplex virus 1 (HSV-1) regulatory protein ICP27 has been reported to bind viral RNA and to interact with the nuclear export adaptor Aly/REF and the major cellular mRNA nuclear export receptor TAP/NXF1. Using in situ hybridization and in vitro export assays, we show here that poly(A)(+) RNA was retained in the nucleus of cells infected with viral ICP27 mutants that either cannot bind RNA or that do not interact with TAP/NXF1. Microarray analysis of nuclear and cytoplasmic RNA fractions demonstrated that efficient export of the majority of viral transcripts requires that ICP27 be able to bind RNA and to interact with TAP/NXF1. We conclude that ICP27 is the major export adaptor for HSV-1 mRNA and that it links bound transcripts to the TAP/NXF1 export receptor.