The double-stranded RNA-binding protein Staufen is incorporated in human immunodeficiency virus type 1: Evidence for a role in genomic RNA encapsidation

Human Staufen (hStau), a double-stranded RNA (dsRNA)-binding protein that i s involved in mRNA transport, is incorporated in human immunodeficiency vir us type 1 (HIV-1) and in other retroviruses, including HIV-2 and Moloney mu rine leukemia virus. Sucrose and Optiprep gradient analyses reveal cosedime ntation of hStau with purified HIV-1, while subtilisin assays demonstrate t hat it is internalized. hStau incorporation in HIV-1 is selective, is depen dent on an intact functional dsRNA-binding domain, and quantitatively corre lates with levels of encapsidated HIV-1 genomic RNA. By coimmunoprecipitati on and reverse transcription-PCR analyses, we demonstrate that hStau is ass ociated with HIV-1 genomic RNA in HIV-1-expressing cells and purified virus , Overexpression of hStau enhances virion incorporation levels, and a corre sponding, threefold increase in HIV-1 genomic RNA encapsidation levels. Thi s coordinated increase in hStau and genomic RNA packaging had a significant negative effect on viral infectivity, This study is the first to describe hStau within HIV-1 particles and provides evidence that hStau binds HIV-1 g enomic RNA, indicating that it may be implicated in retroviral genome selec tion and packaging into assembling virions.