Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) functions in a position-dependent manner

Area of Science:

• Molecular Virology
• RNA Transport Mechanisms
• Retroviral Gene Expression

Background:

• The Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) is a cis-acting RNA element in the 3' untranslated region (UTR).
• CTE can functionally replace the Rev/RRE regulatory system in human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV).
• Previous studies indicated the importance of CTE's genomic position in the SIV context.

Purpose of the Study:

• To investigate the significance of CTE's genomic position for its function within the MPMV genome.
• To elucidate the relationship between CTE, the polyadenylation signal, and viral replication.

Main Methods:

• Generation of MPMV molecular clones with deleted or displaced CTE.
• Single-round replication assays, Western blot, and slot blot analyses.
• Manipulation of CTE and polyadenylation (poly(A)) signal proximity.

Main Results:

• Deletion or displacement of CTE from the 3' UTR abrogated virus replication, Gag/Pol protein production, and nucleocytoplasmic transport of viral mRNA.
• Restoration of CTE to its original 3' terminal position rescued viral replication and RNA transport.
• CTE's function was lost with increasing distance from the poly(A) signal, and proximity was restored upon repositioning the poly(A) signal.

Conclusions:

• The 3' terminal position of CTE is critical for its function in the MPMV genome.
• Close proximity between CTE and the poly(A) signal is essential for efficient CTE function.
• A functional interaction between CTE and the polyadenylation machinery is suggested.