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Human PAF1 inhibition of HIV-1

Authors
Journal
Retrovirology
1742-4690
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Volume
10
Identifiers
DOI: 10.1186/1742-4690-10-s1-p39
Keywords
  • Poster Presentation
Disciplines
  • Biology
  • Engineering
  • Medicine

Abstract

Human PAF1 inhibition of HIV-1 POSTER PRESENTATION Open Access Human PAF1 inhibition of HIV-1 Ana Guerrero Alonso*, Kelly Marno, William Ogunkolade, Julieta Diaz-Delfin, Eithne O’Sullivan, Áine McKnight From Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Cambridge, UK. 16-18 September 2013 Background The Polymerase II-Associated Factor 1 (PAF1) is a cellular protein with essential roles in transcription activation and repression, polyA tail cleavage, regulation of RNA poly- merase elongation, regulation of gene expression, cell cycle control and mRNA quality surveillance[1]. It is part of a multicomponent complex together with other cellular proteins including SKI8, LEO1, CDC73, RTF1 and CTR9 [1]. We described that PAF1 has antiviral effect against HIV-1 that manifests early in the replication cycle [2]. Marazzi et al. described that PAF1 also inhibits influenza virus infection suggesting that PAF1 could have a broad antiviral activity [3]. Localisation of endogenous PAF1 is mainly in the nucleus but also in the cytoplasm. We pro- pose three hypotheses: that PAF1 acts from the cytoplasm or the nucleus or both. Materials and methods To investigate a link between the antiviral function and cellular localisation of PAF1, human PAF1 mutants were engineered with altered nuclear localization signals. Wild type and mutant PAF1 constructs were charac- terised by confocal imaging, cellular fractionation and ability to inhibit HIV-1, 2 and SIV. Viral infectivity was measured by quantitative RT-PCR of early and late HIV-1 transcripts as well as focus forming units. Results Results describing the requirements for specific cellular localisations of PAF1 for viral inhibition will be presented. Conclusion Understanding the mechanism by which PAF1 modu- lates HIV-1 infection could unravel novel drug targets not only against HIV-1 infection but possibly against other viruses. Published: 19 September 2013 References 1. Tomson BN, Arndt KM: The many role

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