Distinct domains in herpes simplex virus type 1 US11 protein mediate post-transcriptional transactivation of human T-lymphotropic virus type I envelope glycoprotein gene expression and specific binding to the Rex responsive element

Herpes simplex virus type 1 (HSV-1) US 1 1 protein is an RNA-binding protein which is able to mediate post-transcriptional transactivation of human T-lymphotropic virus type I (HTLV-I) envelope glycoprotein gene expression by interacting with the Rex responsive element (XRE) located at the 3' end of the env mRNA, In view of this functional activity, and because US 1 1 protein is capable of substituting for HTLV-I Rex protein, it was hypothesized that US11 protein should exhibit at least two functional domains, an RNA-binding domain for specific interaction with the target RNA, and an effector domain involved in transport and translation of this mRNA, Recombinant US11 wild-type and deleted proteins were tested for their ability (i) to bind to the XRE and to HSV-1 UL34 RNA, the natural target of US11 protein, and (ii) to transactivate HTLV-I env gene expression, The C-terminal half of US11 protein, consisting of 20-24 XPR repeats, was necessary and sufficient to mediate RNA-binding with a high affinity and specificity, Structure prediction analyses showed the likely conformation of this domain to be that of a polyproline type II helix, Localized within the first 40 amino acids of the N-terminal region of US11 protein was the effector domain, deletion of which created US11(Delta 1-40), a trans-dominant negative mutant, These results demonstrate structural differences between US11 protein and proteins like Rex and Rev, despite their functional similarities.