RTE and CTE mRNA export elements synergistically increase expression of unstable, rev-dependent HIV and SIV mRNAs

Author:

Smulevitch, S.

Bear, J.

Alicea, C.

Rosati, M.

Jalah, R.

Zolotukhin, A. S.

Von Gegerfelt, A.

Michalowski, D.

Moroni, C.

Pavlakis, G. N.

Felber, B. K.
Author Address

NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. Univ Basel, Inst Med Mikrobiol, Basel, Switzerland.;Felber, BK, NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA.;smulevit@hotmail.com bear@ncifcrf.gov calicea@ncifcrf.gov rosati@ncifcrf.gov rjalah@ncifcrf.gov zolotukh@ncifcrf.gov vongeger@ncifcrf.gov michalowskid@missouri.edu Christoph.Moroni@unibas.ch pavlakis@ncifcrf.gov felber@ncifcrf.gov

Abstract:

Studies of retroviral mRNA export identified two distinct RNA export elements utilizing conserved eukaryotic mRNA export mechanism(s), namely the Constitutive Transport Element (CTE) and the RNA Transport Element (RTE). Although RTE and CTE are potent in nucleocytoplasmic mRNA transport and expression, neither element is as powerful as the Rev-RRE posttranscriptional control. Here, we found that whereas CTE and the up-regulatory mutant RTEm26 alone increase expression from a subgenomic gag and env clones, the combination of these elements led to a several hundred-fold, synergistic increase. The use of the RTEm26-CTE combination is a simple way to increase expression of poorly expressed retroviral genes to levels otherwise only achieved via more cumbersome RNA optimization. The potent RTEm26-CTE element could be useful in lentiviral gene therapy vectors, DNA-based vaccine vectors, and gene transfer studies of other poorly expressed genes.

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