Room: Roger Guindon Hall, Room 4214 (office), 4210 (lab)
Office: 613-562-5800 ext. 8215
Work E-mail: Marceline.Cote@uottawa.ca
The overarching goal of the Côté laboratory is to improve our understanding of host-pathogen interactions during infection by emerging viruses, towards the development of novel host- and/or viral-oriented antiviral therapeutics. In the laboratory, we combine virological, chemical biology, and genetic approaches to identify host proteins critical for viral infection that can be targeted to block virus spread. We are particularly interested in acquiring a detailed understanding of the entry pathways of filoviruses (Ebola and Marburg viruses), arenaviruses (Lassa fever virus), and coronaviruses (Severe acute respiratory syndrome virus and Middle East respiratory syndrome virus).
Ebola virus entry pathway
Ebola virus (EboV) is an enveloped, non-segmented, negative-stranded RNA virus member of the filoviridae family. EboV is the causative agent of unpredictable severe hemorrhagic fever outbreaks in humans and non-human primates with lethality rates that can reach 90%, against which there are currently no approved effective antiviral therapies. The increasing numbers of EboV outbreaks and the ease of transmission demonstrate the urgent need for the development of new antivirals. The discovery of the long-sought EboV receptor, the protein Niemann-Pick C1 (NPC1) localized within late endosomes/lysosomes, suggests that the virus requires internalization and regulated endomembrane trafficking to reach vesicles containing NPC1 to enter the host cells. This complex entry pathway involves multiple direct and indirect orchestrated interactions with host proteins, offering several opportunities for therapeutic interventions.
Using viral pseudotypes, high-throughput screening of small molecule inhibitors, genome editing strategies, and live-cell imaging technologies, we are interested in identifying new host factors interfering with EboV trafficking and characterizing their roles in viral entry. By using small molecules as biological probes for investigating the essential roles of host proteins in infection, our studies will not only provide a better understanding of EboV entry mechanism, but these small molecules can serve as starting points for the development of new antiviral drugs.
Ebola virus Research
- Côté M*, Misasi J*, Ren T*, Bruchez A*, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J
Small molecule inhibitors reveal Niemanm-Pick C1 is essential for Ebola virus infection. Nature. 2011 Aug;477(7364):344-8 * contributed equally
- Lee K, Ren T, Côté M, Gholamreza B, Misasi J, Bruchez A, Cunningham J
Inhibition of Ebola virus infection: identification of Niemann-Pick C1 as the target by optimization of a chemical probe. ACS Med. Chem. Lett. 2013; 4(2):239-43.
- Misasi J, Chandran K, Yang JY, Considine B, Filone CM, Côté M, Sullivan N, Fabozzi G, Hensley L, Cunningham J
Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences. J Virol. 2012 Mar; 86(6):3284-92
- Côté M, Cunningham J
L’entrée du virus Ébola et Marburg : interaction entre la glycoprotéine virale et les facteurs cellulaires. Virologie. 2012; 16(3):168-77
- Côté M*, Zheng YM*, Liu SL
Membrane fusion and cell entry of XMRV are pH-independent and modulated by the envelope glycoprotein’s cytoplasmic tail. PLoS One. 2012; 7(3):e33734 * contributed equally
- Côté M*, Zheng YM*, Li K, Xian SH, Albritton LM, Liu SL
Critical role of leucine-valine change in distinct low pH requirements for membrane fusion between two related retrovirus envelopes. J Biol Chem. 2012 Mar; 287(10):7640-51 * contributed equally
- Côté M, Zheng YM, Liu SL
Single residues in the surface subunit of oncogenic sheep retrovirus envelopes distinguish receptor mediated triggering for fusion at low pH and infection. Virology. 2011 Sept; 421(2):173-83
- Côté M, Zheng YM, Liu SL
Receptor binding and low pH coactivate oncogenic retrovirus envelope-mediated fusion. J Virol. 2009 Nov;83(22):11447-55
- Côté M, Kucharski TJ, Liu SL
Enzootic nasal tumor virus envelope requires a very acidic pH for fusion activation and infection. J Virol. 2008 Sep;82(18):9023-34
- Côté M, Zheng YM, Albritton LM, Liu SL
Fusogenicity of jaagsiekte sheep retrovirus envelope protein is dependent on low pH and is enhanced by cytoplasmic tail truncations. J Virol. 2008 Mar;82(5):2543-54