4.4 Article

Lentiviral RNAs can use different mechanisms for translation initiation

Journal

BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 36, Issue -, Pages 690-693

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BST0360690

Keywords

eukaryotic initiation factor 4G (eIF4G); Gag; internal ribosome entry site (IRES); lentivirus; translation; 5'-untranslated region (5'-UTR)

Funding

  1. MENRT (Ministere de I'Education Nationale, de la Recherche et de la Technologie)
  2. ANR (Agence Nationale de la Recherche)
  3. ANRS (Agence Nationale de Recherche sur le Sida et les Hepatites Virales)
  4. Inserm
  5. SIDACTION

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The full-length genomic RNA of lentiviruses can be translated to produce proteins and incorporated as genomic RNA in the viral particle. interestingly, both functions are driven by the genomic 5'-UTR (5'-untranslated region), which harbours structural RNA motifs for the replication cycle of the virus. Recent work has shown that this RNA architecture also functions as an IRES (internal ribosome entry site) in HIV-1 and -2,and in SIV(simian immunodeficiency virus). in addition, the IRES extends to the gag coding region for all these viruses and this leads to the synthesis of shorter isoforms of the Gag polyprotein from downstream initiation codons. In the present study, we have investigated how different members of the lentivirus family (namely HIV-1 and -2, and SIV) can initiate protein synthesis by distinct mechanisms. For this, we have used the competitive reticulocyte lysate that we have recently described. our results show that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to use exclusively an IRES mechanism.

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