RNA trafficking signals in human immunodeficiency virus type 1

Intracellular trafficking of retroviral RNAs is a potential mechanism to ta rget viral gene expression to specific regions of infected cells. Here we s how that the human immunodeficiency virus type 1 (HIV-1) genome contains tw o sequences similar to the hnRNP A2 response element (A2RE), a cis-acting R NA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized ext ensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, w ithin the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and , in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transpor t is microtubule and hnRNP A2 dependent. Differentially labelled gag and vp r RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the sam e RNA trafficking granules and are cotransported to the periphery of the ce ll. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is p roposed, and the role of RNA trafficking in targeting HIV gene expression i s discussed.