Our lab focuses on understanding virus-host interactions. Because of the strict dependence of viruses on the molecular machineries of their hosts, complex strategies have evolved to enable viruses to control the cell to their advantage. In a way, viruses can be thought of as molecular tinkerers that became engineers. As such, viruses provide unique opportunities to peer into the inner workings of the cell: by understanding the mechanisms by which viruses control their host cells, we get valuable insights into basic cell biology.
To understand how viruses use the cellular components to translate, fold and modify their proteins, we use cutting edge high-throughput methods, including ribosome profiling and CRISPR-based genetic screens. Ribosome profiling sheds light on the translational engagement of both viral and host transcripts during the course of the infection, providing a unique perspective on the translational overhaul occurring during viral infections. The CRISPR-based genetic screens are designed to single out host factors that promote or limit infection. This strategy has the power to reveal promising new avenues for the development of antivirals targeting the host, thereby circumventing the problem of virus-acquired drug resistance.
Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, Mancia Leon WR, Krencik R, Ullian EM, Spatazza J, Pollen AA, Mandel-Brehm C, Nowakowski TJ, Kriegstein AR, DeRisi JL. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408-14413. Epub 2016 Nov 29. PMID: 27911847
Arias C, Weisburd B, Stern-Ginossar N, Mercier A, Madrid AS, Bellare P, Holdorf M, Weissman JS, Ganem D. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features. PLoS Pathog. 2014 Jan;10(1):e1003847. doi: 10.1371/journal.ppat.1003847. PMID: 24453964.
Mercier A, Arias C, Madrid AS, Holdorf MM, Ganem D. Site-specific association with host and viral chromatin by Kaposi's sarcoma-associated herpesvirus LANA and its reversal during lytic reactivation. J Virol. 2014 Jun;88(12):6762-77. doi: 10.1128/JVI.00268-14. PMID: 24696474
Arias C, Walsh D, Harbell J, Wilson AC, Mohr I. Activation of host translational control pathways by a viral developmental switch. PLoS Pathog. 2009 Mar;5(3):e1000334. doi: 10.1371/journal.ppat.1000334. PMID: 19300492
Walsh D, Arias C, Perez C, Halladin D, Escandon M, Ueda T, Watanabe-Fukunaga R, Fukunaga R, Mohr I. Eukaryotic translation initiation factor 4F architectural alterations accompany translation initiation factor redistribution in poxvirus-infected cells. Mol Cell Biol. 2008 Apr;28(8):2648-58. doi: 10.1128/MCB.01631-07. PMID: 18250159