Post-transcriptional Regulation of HTLV Gene Expression: Rex to the Rescue.

Donna M D’Agostino,Vincenzo Ciminale,Maria Grazia Romanelli,Ilaria Cavallari

doi:10.3389/fmicb.2019.01958

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) and other members of the Deltaretrovirus genus code for a regulatory protein named Rex that binds to the Rex-responsive element present on viral mRNAs. Rex rescues viral mRNAs from complete splicing or degradation and guides them to the cytoplasm for translation. The activity of Rex is essential for expression of viral transcripts coding for the virion components and thus represents a potential target for virus eradication. We present an overview of the functional properties of the HTLV-1 and HTLV-2 Rex proteins (Rex-1 and Rex-2), outline mechanisms controlling Rex function, and discuss similarities and differences in the sequences of Rex coded by HTLV-1, -2, -3, and -4 that may influence their molecular anatomy and functional properties.

Highlights

Human T-lymphotropic virus type 1 (HTLV-1) infects approximately 10 million persons worldwide (Willems et al, 2017)
A search for novel monocistronic HTLV-1 transcripts coding for only Tax or Rex revealed the production of mRNAs that contain exons 1 and 2 linked to splice acceptors (SA) located upstream (C, Ca) or downstream (3a) of the canonical exon 3 SA; the use of these SA results in insertion or deletion of amino acids in the Rex open reading frames (ORFs) just after the nucleolar localization signal (NLS)/RNA binding domain (RBD) (Figure 3A; Rende et al, 2015)
Viral replication is considered to be a key factor that drives the inflammatory response to HTLV-1, with risk for developing tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM), and ensures the generation of a vast population of infected cells at risk for neoplastic transformation (Bangham, 2018)

Summary

Introduction

Human T-lymphotropic virus type 1 (HTLV-1) infects approximately 10 million persons worldwide (Willems et al, 2017). Met-79 is present in all of the Rex ORFs examined in Supplementary Figure 1, so all of these viruses should be able to express p21Rex. In HTLV-2, spliced mRNAs 1-3 and 1-B code for truncated Rex-2 proteins named p22/p20Rex and p17Rex (Ciminale et al, 1997; Figure 3B).

Results

Conclusion