Domain- and nucleotide-specific Rev response element regulation of feline immunodeficiency virus production

Abstract

Computational analysis of feline immunodeficiency virus (FIV) RNA sequences indicated that common FIV strains contain a rev response element (RRE) defined by a long unbranched hairpin with 6 stem-loop sub-domains, termed stem-loop A (SLA). To examine the role of the RNA secondary structure of the RRE, mutational analyses were performed in both an infectious FIV molecular clone and a FIV CAT-RRE reporter system. These studies disclosed that the stems within SLA (SA1, 2, 3, 4, and 5) of the RRE were critical but SA6 was not essential for FIV replication and CAT expression. These studies also revealed that the secondary structure rather than an antisense protein (ASP) mediates virus expression and replication in vitro. In addition, a single synonymous mutation within the FIV-RRE, SA3/45, reduced viral reverse transcriptase activity and p24 expression after transfection but in addition also showed a marked reduction in viral expression and production following infection.

The Molecular Biology of Feline Immunodeficiency Virus (FIV)

“…In the primate lentiviruses the RRE overlaps the middle of the env ORF, making mutagenesis of the RRE difficult without disrupting Env function, but in FIV the RRE resides at the very 3′end of the env ORF, making mutagenic studies possible. The RRE folds into a conserved stem-loop of around 150 nts and it appears that the entire structure except for the very tip (stem 6 and the loop) is critical for Rev function: structural perturbation of any of the other 5 stems disrupts FIV replication [ 101 ].…”