Abstract
BackgroundRetroviruses selectively encapsidate two copies of their genomic RNA, the Gag protein binding a specific RNA motif in the 5' UTR of the genome. In human immunodeficiency virus type 2 (HIV-2), the principal packaging signal (Psi) is upstream of the major splice donor and hence is present on all the viral RNA species. Cotranslational capture of the full length genome ensures specificity. HIV-2 RNA dimerisation is thought to occur at the dimer initiation site (DIS) located in stem-loop 1 (SL-1), downstream of the main packaging determinant. However, the HIV-2 packaging signal also contains a palindromic sequence (pal) involved in dimerisation. In this study, we analysed the role of the HIV-2 packaging signal in genomic RNA dimerisation in vivo and its implication in viral replication.ResultsUsing a series of deletion and substitution mutants in SL-1 and the Psi region, we show that in fully infectious HIV-2, genomic RNA dimerisation is mediated by the palindrome pal. Mutation of the DIS had no effect on dimerisation or viral infectivity, while mutations in the packaging signal severely reduce both processes as well as RNA encapsidation. Electron micrographs of the Psi-deleted virions revealed a significant reduction in the proportion of mature particles and an increase in that of particles containing multiple cores.ConclusionIn addition to its role in RNA encapsidation, the HIV-2 packaging signal contains a palindromic sequence that is critical for genomic RNA dimerisation. Encapsidation of a dimeric genome seems required for the production of infectious mature particles, and provides a promising therapeutic target.
Highlights
Retroviruses selectively encapsidate two copies of their genomic RNA, the Gag protein binding a specific RNA motif in the 5' UTR of the genome
The sequence involved in the formation of stem B is part of a 10 nt palindrome, located within the packaging signal Psi (Ψ), and which has been suggested to play a role in RNA dimerisation in vitro [21]
In human immunodeficiency virus type 2 (HIV-2), initiation of dimerisation has been postulated to occur at the dimer initiation site (DIS), a palindrome located at the top of stem-loop 1 (SL-1) (Fig. 1B) [21,22]
Summary
Retroviruses selectively encapsidate two copies of their genomic RNA, the Gag protein binding a specific RNA motif in the 5' UTR of the genome. In human immunodeficiency virus type 2 (HIV-2), the principal packaging signal (Psi) is upstream of the major splice donor and is present on all the viral RNA species. Encapsidation is very specific, as the virus has to select and package the full length genomic RNA over the vast excess of cellular and subgenomic RNA species. In the case of HIV-2, the process is less well understood as the main packaging determinant (Psi or Ψ) appears to be located upstream of the major splice donor [7]. In a study to further map the HIV-2 encapsidation signal, a 28 nucleotides (nt) sequence upstream of the splice donor was identified as being required for HIV-2 RNA packaging [8]. The structural Gag protein is translated from the full length RNA and encapsidates the RNA from the same pool from which it was translated [8,9]
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