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) US11 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 US11 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(delta1-40), a trans-dominant negative mutant. These results demonstrate structural differences between US11 protein and proteins like Rex and Rev, despite their functional similarities.
Immuno-Virologie Moléculaire et Cellulaire CNRS UMR5537, Faculté de Médecine Lyon-R.T.H. Laennec, Lyon, France.
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N
Schaerer-Uthurralt
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M
Erard
K
K
Kindbeiter
J J
JJ
Madjar
J J
JJ
Diaz
D001665:Binding Sites; D003198:Computer Simulation; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000235:genetics*; D016370:Gene Products, rex / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics*; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D015686:Gene Products, env; D016370:Gene Products, rex; D006023:Glycoproteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins