SCIENCE-JOBS-DE

(PhD Student Position HIV research) (Frankfurt​)

Characterisation of the Vpx-mediated antagonism of the interferon-induced antiviral state in macrophages

Macrophages present an important cell type for HIV-1 infection and may serve as a latent reservoir for HIV-1 in vivo. Type I interferons can induce a potent antiviral state in macrophages preventing early steps of the HIV-1 infection cycle at the stage of reverse transcription. The host factors responsible for this block and the underlying mechanisms are unknown. Infection of HIV-1 in the presence of type I interferons can be augmented by the provision of the SIVsmm/HIV-2 accessory protein Vpx, which was recently shown to antagonize SAMHD1, a resistance factor that prevents cells from HIV-1 infection. However, the Vpx mediated rescue of HIV-1 from the IFN-induced antiviral state in macrophages appears to be independent of SAMHD1, suggesting additional Vpx targets.
The aim of the project is to characterize Vpx-mediated rescue of HIV-1 infection from the type I IFN induced block. This will be achieved by several approaches including the generation of Vpx point mutants that will be tested for their activity to rescue HIV-1 from the antiviral state, to correlate the phenotypes of these mutants to the recently published Vpx structure and to address the question whether SAMHD1 antagonism and counteraction of the IFN-induced antiviral state are genetically separable. The long-term goal is to identify the mechanism(s) of how Vpx counteracts the IFN-induced antiviral state to enhance HIV-1 infection and to identify participating host factors in the block as well as in the counteraction process.

The successful candidate will have an outstanding study record and practical experience in molecular biology, biochemistry and immunology, preferably with an excellent diploma thesis or equivalent in the field of virology or immunology. We expect a strong interest in HIV-1 research, the ability to perform solid, well-controlled experiments, and a very high level of motivation. We offer interesting research topics with high biomedical relevance in a stimulating and interactive scientific environment at an internationally competitive level.

Please send your applications preferably by email with full CV including an abstract of your Diploma/ Masters thesis, list of publications and short letter of motivation until July 4, 2014 to:
Dr. Torsten Schaller, Institute of Medical Virology, National Reference Center for Retroviruses, Department of Infectious Diseases, Virology, Johann Wolfgang Goethe-University Frankfurt a.M., Paul-Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany.Current E-Mail address: Torsten.Schaller@kcl.ac.uk

Relevant Literature
Schaller et al., Frontiers in Microbiology 2014 - Recent review on Vpx
Reinhard et al., Retrovirology 2014 - SAMHD1 independent HIV-1 rescue by Vpx in DCs
Schwefel et al., Nature 2014- Co-crystal structure of Vpx/SAMHD1/DCAF1
Goujon et al., Nature 2013- Mx2 is an IFN induced gene that blocks HIV-1
Kane et al., Nature 2013- Mx2 is an IFN induced gene that blocks HIV-1
Goujon and Schaller et al., Retrovirology 2013-SAMHD1 independent IFN induced genes block HIV-1
Pertel et al., Retrovirology 2011-Vpx counteracts the antiviral state in DCs
Goujon et al., Journal of Virology 2010- IFNÎą blocks HIV-1 at reverse transcription in macrophages


Torsten Schaller
torsten.schaller@kcl.ac.uk
Institute of Medical Virology at the University Hospital Frankfurt, Frankfurt a.M., Germany
Frankfurt

Ansprechpartner: Torsten Schaller, Torsten.Schaller@kcl.ac.uk