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ARMOR (until 2023)

ARMOR

Arbovirus Molecular research

Team Arbovirus Molecular research (ARMOR) focuses on studying the genetic/molecular basis influencing dsRNA arbovirus (particularly viruses belonging to genus Orbivirus, family Sedoreoviridae, order Reovirales) replication in mammalian /arthropod-vector cells. Being an arbovirus depends on the success of interactions between the virus, the vector and the host, which together constitute the ‘epidemiological triangle’.
Orbiviruses are animal pathogens which are usually transmitted between their vertebrate hosts (ruminants, equids, humans, birds…) by the bites of midges, mosquitoes, ticks or phlebotomine flies, in which they also replicate. Bluetongue virus (BTV) is the type-species of the genus Orbivirus. The ‘classical’ serotypes of BTV (serotypes 1-24) are transmitted between their ruminant hosts by the bite of adult females of several Culicoides vector-species, in which the virus replicates efficiently. The classical BTV serotypes are poorly and inefficiently transmitted by direct contact from infected to in-contact host animals. Since 2008, several ‘atypical’ non-vectored bluetongue viruses have been discovered (belonging to at least 12 previously unknown serotypes, 25 to 36) that do not replicate in adult Culicoides, in cell lines derived from known Culicoides vector species, or in other arthropod vectors (including ticks and mosquitoes) and are strictly transmitted by direct contact between animal hosts. Their direct transmission from experimentally infected to in-contact animals is very efficient, suggesting they have acquired novel functions supporting this mode of transmission in the vertebrate hosts.
Our studies endeavours to provide insights into what makes orbiviruses effective arboviruses. The team was involved to the H2020 PALE-Blu project (August 2017-January 2022), coordinating the project and as a partner leading three major work packages (https://www.paleblu.eu).

Our research themes:

We investigate: (i) the coding strategies of orbiviruses in order to discover and functionally characterise novel virally-encoded proteins both in mammalian and arthropod cells, (ii) the orbivirus-related genetic controls of infection and replication in arthropod cells (e.g. the vector's innate immune response and virus countermeasures), (iii) the mechanisms underlying restricted replication of atypical BTV in vector-derived cells and the mechanisms facilitating direct transmission and (iv) antiviral strategies for orbiviruses.

Figures

Figure-NS5.png
Expression of NS5 in mammalian/insect cells infected with various orbiviruses. In BTV and AHSV, the protein is both cytoplasmic and nucleolar, while in the tick-borne KEMV NS5 is mainly cytoplasmic.
Figure-NS5nuc.png
NS5 disrupts nucleoli of BSR cells infected with BTV (left panel), interacts with cellular ZBP-1 (middle panel), NS5 interacts with supercoiled DNA in a gel shit assay (right panel).
Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells. 2023
 
Figure-CineticRepli.png
Genome segments 1, 2 and 3 involved in restricted replication of BTV-26 in Culicoides-derived cells
Figure-BTV26-VP2.png
Left panel: BTV-26 and BTV-1 bind KC cells efficiently. Right panel: stable stem-loop structures of mRNA encoding BTV-26 VP2 involved in ribosome jump resulting in a shorter form of VP2 in KC cells.
Uncovering the Underlying Mechanisms Blocking Replication of Bluetongue Virus Serotype 26 (BTV-26) in Culicoides Cells. 2023

Our members:

  • Head
    • ATTOUI Houssam (INRAE)
  • Scientific Staff
    • MONSION Baptiste (INRAE, senior scientist)
    • MOHD JAAFAR Fauziah (ANSES, senior scientist)
  • PhD Candidate
    • MIGNE Camille (EnvA)

Most recent publications:

  1. Migné CV, Heckmann A, Monsion B, Mohd Jaafar F, Galon C, Rakotobe S, Bell-Sakyi L, Moutailler S, Attoui H. Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR(-/-) Mice. Int J Mol Sci. 2024 Mar 9;25(6):3177. doi: 10.3390/ijms25063177.
  2. Beaud G, Costa F, Klonjkowski B, Piumi F, Coulpier M, Drillien R, Monsion B, Mohd Jaafar F, Attoui H. Vaccinia Virus Defective Particles Lacking the F17 Protein Do Not Inhibit Protein Synthesis: F17, a Double-Edged Sword for Protein Synthesis? Int J Mol Sci. 2024 Jan 23;25(3):1382. doi: 10.3390/ijms25031382.
  3. Mohd Jaafar F, Belhouchet M, Monsion B, Bell-Sakyi L, Mertens PPC, Attoui H. Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses. Viruses. 2023 Sep 12;15(9):1908. doi: 10.3390/v15091908.
  4. Mohd Jaafar F, Monsion B, Mertens PPC, Attoui H. Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells. Int J Mol Sci. 2023 Apr 6;24(7):6845. doi: 10.3390/ijms24076845.
  5. Monsion B, Mohd Jaafar F, Mertens PPC, Attoui H. Uncovering the Underlying Mechanisms Blocking Replication of Bluetongue Virus Serotype 26 (BTV-26) in Culicoides Cells. Biomolecules. 2023 May 23;13(6):878. doi: 10.3390/biom13060878.