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2016-05-01Dissertation DOI: 10.25646/5357
Characteristics and Relevance of the Interaction between Staufen-1 and Rev-related retroviral Proteins
dc.contributor.authorMostafa, Saeed Mostafa Ameen
dc.date.accessioned2018-05-08T04:45:38Z
dc.date.available2018-05-08T04:45:38Z
dc.date.created2016-09-06
dc.date.issued2016-05-01none
dc.identifier.otherhttp://edoc.rki.de/documents/dissertationen/mostafa-saeed-mostafa-ameen-2016-05-01/PDF/mostafa.pdf
dc.identifier.urihttp://edoc.rki.de/176904/5432
dc.description.abstractStaufen-1 is a cellular protein involved in subcellular RNA transport and the translation and packaging of retroviral RNA into viral particles. In this study, several aspects of the impact of Staufen-1 on SIVmac, HIV-1 and HERV-K(HML-2) particle production were investigated. The results obtained show that, similar to the situation with HIV-1 and HERV-K(HML-2), overexpression of Staufen-1 also enhances SIVmac particle production. However, the 3-4-fold increase in SIVmac particle production is slightly (2x) lower than that seen with HIV-1 and significantly lower than the 20-30-fold boost of HERV-K(HML-2) production. This enhancement is not dependent on the general level of expression but appears to be an intrinsic property of the virus. As expected, downregulation of endogenous Staufen-1 expression using Staufen-1 specific shRNAs negatively affected SIVmac particle production. On the other hand, an excessive overexpression of Staufen-1 decreases HIV-1, but not HERV-K(HML-2) or SIVmac particle production, indicating that the optimal levels of cellular Staufen-1 are different for these viruses. Using luciferase reporter viruses, differences between the genera were also found with regard to the effect of Staufen-1 on RNA shuttling and translation. Whereas Staufen-1 overexpression enhances HERV-K(HML-2) production at these stages of replication, the opposite has been observed for the two lentiviruses. The positive net effect of Staufen-1 overexpression on HIV-1 and SIVmac particle production therefore appears to result primarily from improved packaging and assembly while, for HERV-K(HML-2), RNA transport and translation are also enhanced. Furthermore, similar to the situation with HIV-1 Rev, Staufen-1 interacts directly with SIVmac Rev, with the Staufen-1 RBD3 domain being involved in this binding. HERV-K(HML-2) Rec has a significant impact on the Staufen-1 mediated enhancement of particle production. Nevertheless, the fact that this impact is not completely abrogated by the lack of Rec indicates the existence of an additional, Rec-independent mechanism of HERV-K(HML-2) enhancement by Staufen-1. In addition, overexpression of Rec promotes HERV-K(HML-2) production. Finally, the study confirms previous reports that show a strong boost in particle production by Staufen-1 overexpression and the functional substitution of Rec by HIV-1 Rev, SIVmac Rev and HTLV Rex proteins. In contrast Np9, the protein produced by type I HERV-K(HML-2), cannot functionally substitute Rec.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subject.ddc610 Medizin
dc.titleCharacteristics and Relevance of the Interaction between Staufen-1 and Rev-related retroviral Proteins
dc.typedoctoralThesis
dc.identifier.urnurn:nbn:de:0257-10046759
dc.identifier.doihttp://dx.doi.org/10.25646/5357
dc.date.accepted2016-05-01
local.edoc.type-nameDissertation
local.edoc.universityFreie Universität Berlin

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