Dr Pierre Maillard
UCL Excellence Fellow
Research in the Maillard lab aims to understand the cell types and contexts in which antiviral RNA interference plays a role in mammals.
My research interests focus on the study of a new layer of mammalian innate immunity based on RNA interference (RNAi). This mechanism is a well-established antiviral defence in plants and invertebrates in which long double-stranded RNA (dsRNA) derived from viral replication is cleaved by the enzyme Dicer into small interfering RNA (siRNA). These small RNAs are loaded into an effector complex and guide the cleavage of target RNAs such as the viral genomes and viral transcripts.
During my postdoctoral studies, I opted to explore the potential existence of antiviral RNAi in mammalian cells. I uncovered that this mechanism of antiviral defence is intact and effective in mouse embryonic stem cells but is highly reduced in differentiated cells. In these latter cells, the introduction of long dsRNA triggers RNAi but it is inhibited by the interferon pathway. My research now aims to characterise the cell types and contexts in which this ancestral mechanism plays a role in the mammalian antiviral defence system.
- Van der Veen AG, Maillard PV, Marten Schmidt J, Lee SA, Deddouche-Grass S, Borg A., Kjaer S., Sniders AP, Reis e Sousa C. The RIG-I-like receptor LGP2 inhibits Dicer- dependent processing of long double-stranded RNA and blocks RNA interference in mammalian cells. EMBO J. 2018;37(4)
- Maillard PV, Van der Veen AG, Deddouche-Grass S, Rogers NC, Merits A, Reis E Sousa C. Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells. EMBO J. 2016;35:2505-2518
- van der Veen AG, Maillard PV, Reis e Sousa C. Drosha cuts the tethers of myelopoiesis. Nat Immunol. 2015;16:1110-2
- Deddouche S, Goubau D, Rehwinkel J, Chakravarty P, Begum S, Maillard PV, Borg A, Matthews N, Feng Q, van Kuppeveld FJ, Reis e Sousa C. Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells. Elife. 2014;3:e01535
- Maillard PV, Ciaudo C, Marchais A, Li Y, Jay F, Ding SW, Voinnet O. Antiviral RNA interference in mammalian cells. Science. 2013;342:235-8
- Maillard PV, Zoete V, Michielin O, Trono D. Homology-based identification of capsid determinants that protect HIV1 from human TRIM5α restriction. J Biol Chem. 2011;286:8128-40
- Maillard PV, Ecco G, Ortiz M, Trono D. The specificity of TRIM5 alpha-mediated restriction is influenced by its coiled-coil domain. J Virol. 2010 Jun;84:5790-801
- Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T, Maillard PV, Layard-Liesching H, Verp S, Marquis J, Spitz F, Constam DB, Trono D. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010;463:237-40
- Diaz-Griffero F, Perron M, McGee-Estrada K, Hanna R, Maillard PV, Trono D, Sodroski J. A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus. Virology. 2008;378:233-42
- Maillard PV, Reynard S, Serhan F, Turelli P, Trono D. Interfering residues narrow the spectrum of MLV restriction by human TRIM5alpha. PLoS Pathog. 2007;3:e200.