Role of RNA helicases in HIV-1 replication

Abstract

Viruses are replication competent genomes which are relatively gene-poor. Even the largest viruses (i.e. Herpesviruses) encode only slightly >200 open reading frames (ORFs). However, because viruses replicate obligatorily inside cells, and considering that evolution may be driven by a principle of economy of scale, it is reasonable to surmise that many viruses have evolved the ability to co-opt cell-encoded proteins to provide needed surrogate functions. An in silico survey of viral sequence databases reveals that most positive-strand and double-stranded RNA viruses have ORFs for RNA helicases. On the other hand, the genomes of retroviruses are devoid of virally-encoded helicase. Here, we review in brief the notion that the human immunodeficiency virus (HIV-1) has adopted the ability to use one or more cellular RNA helicases for its replicative life cycle.

Figure 1

Schematic representation of the involvement of cellular RNA helicases in reverse transcription, transcription and post-transcriptional regulation of HIV-1 RNAs. RHA has been found to be a part of the HIV-1 virion and may participate in HIV-1 reverse transcription as well as particle assembly. RHA and RH116 have been reported to participate in HIV-1 transcription through interaction with the viral leader RNA, TAR. DDX1 and DDX3 act with Rev and RRE-containing RNAs for the transport of unspliced and partially spliced HIV-1 RNA from the nucleus to the cytoplasm.

Figure 2

Involvement of Dicer RNA helicase, TRBP and HIV-1 TAR RNA in the biology of the cell's micro RNA pathway. (A) Domain structure of Dicer proteins from mammals and Drosophila. (B) A schematic representation of a potential mechanism for TAR RNA-dependent suppression of Dicer activity. TAR RNA is suggested to bind to TRBP and decoy it from Dicer preventing Dicer-dependent miRNA processing activity.