Rous sarcoma virus direct repeat cis elements exert effects at several points in the virus life cycle

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Rous sarcoma virus (RSV) contains an oncogene, src, flanked by direct repeats (dr1 and dr2).
• These repeats are implicated in cis-acting signals for RNA packaging and cytoplasmic accumulation of unspliced RNA.

Purpose of the Study:

• To investigate the role of dr1 elements in RSV replication and viral particle production.
• To elucidate the impact of dr1 deletions on viral RNA transport, stability, and assembly.

Main Methods:

• Generating RSV mutants with precise deletions of dr1 elements.
• Infecting avian fibroblasts with mutant and wild-type RSV.
• Analyzing viral RNA transport, half-life, and virus particle assembly.

Main Results:

• Mutant RSV lacking dr1 elements expressed src and transformed cells but exhibited significantly reduced virus particle production.
• Replication defects were linked to complex alterations in viral RNA transport, reduced RNA half-life, and impaired virus particle assembly.
• Absence of dr1 elements led to delayed virus spread in cell cultures.

Conclusions:

• The dr1 elements are essential for efficient viral RNA nuclear-cytoplasmic transport, RNA stability, and cytoplasmic utilization of unspliced viral RNA.
• Cell-specific factors may bind to dr1 elements, facilitating these processes.
• Understanding these mechanisms provides insights into defects observed in nonpermissive virus infections in mammalian cells.