Purcell laboratory: Viral RNA elements, regulation of HIV replication, HIV antibody vaccine
The Molecular Virology Laboratory primarily conducts research into the processing of viral messenger RNA (mRNA), with a specialized focus on the human immunodeficiency virus type 1 (HIV-1). The HIV-1 mRNA processing steps include splicing, polyadenylation, transport, cellular localisation, degradation and translation of mRNA into protein. Each step provides a potential means to modulate viral replication, infectivity and pathogenesis, therefore presenting likely targets for antiviral drug design. We study both the HIV-1 encoded and the host cell-derived control mechanisms that determine the efficiency of viral protein expression. RNA-dependent mechanisms, such as RNA interference (RNAi) support cellular antiviral defence pathways that are powerful innate mechanisms that restrict viral replication. We are investigating the convergence of these innate antiviral pathways with adaptive immunity.
From the perspective of virus, our studies of HIV-1 have shown that splicing generates a large array of alternatively spliced mRNAs from the nascent HIV-1 unspliced precursor-mRNA. Many of these mRNAs differ only in their 5' untranslated regions (UTR) and encode the same HIV-1 proteins. We have identified that env mRNAs use a ribosome shunting mechanism during translation, and our studies have identified mRNA elements that control this mechanism. Other aspects that determine translation control, such as the role of viral non-coding introns during viral replication, are also under investigation in our laboratory.
From the cellular aspect, we are focusing on the mechanisms that silence the expression of viral proteins in the astrocytes of brain. Astrocytes are important natural target cells for HIV-1 and their unusual refractory infection serves as a model that may yield novel approaches to restrict HIV-1 in other infected cell populations. Finally, we are applying our understanding of these fine details of HIV-1 and simian immunodeficiency virus (SIV) gene expression to the preparation of novel HIV-1 vaccines.
- Design, development and testing of HIV vaccines
- Passive antibody immunity for use in combination microbicides
- RNA mediated control of HIV-1 gene expression
- Chronic immune activation during treated HIV disease
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For further information about this research, please contact Professor Damian Purcell
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