Characterization of the diversity of and human immune responses against CHIKV strains from Mozambique

• Applicant: Professorin Dr. Christine Goffinet
• Subject Area: Virology ; Immunology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317233047

The high rate of prevalence of CHIKV infection in Southern Mozambique has been established only very recently. There is an urgent need to better understand the genotypic and phenotypic features of CHIKV strains spreading in Mozambique. This German-African cooperation will address key mechanistic and in vivo aspects of CHIKV-host interaction by synergizing individual expertise of both partners, and will foster early career researcher training at the African location. Specifically, we plan to: 1) Describe the diversity of glycoprotein-encoding sequence of CHIKV strains circulating in Mozambique and quantify their relative capacity to promote virus entry and fusion in cell culture. Results of this project arm will reveal the first compilation of glycoprotein sequences of CHIKV strains circulating in Mozambique and the phenotypic features of the respective glycoproteins regarding pharmacological, cellular and immunological inhibition. 2) Explore the pattern of cellular immune response in CHIKV patients using ELISpot assay. Research on correlates of immune protection to CHIKV fever is critical to foster ongoing vaccine development initiatives. We will enroll patients with different clinical severity of CHIKV infection and cellular immune responses of freshly isolated PBMCs of these persons after stimulation with CHIKV E1, E2 and E3-derived peptides by IFN-gamma ELISpot assay. 3) Establish the transcriptional profile in PBMCs from acute, convalescent and chronic patients of CHIKV fever and healthy controls. This analysis will provide the first available complete and quantitative profile of transcriptional activity in the individual patient groups recruited in Southern Mozambique and will be correlated to available clinical data. These results may establish correlates of convalescence versus chronification, and could be harnessed for translational therapeutic applications. 4) Explore potential functional interaction between CHIKV and HIV-1 infection in vivo and ex vivo. The reciprocal impact of HIV-1 and CHIKV infection in vivo has been only poorly described to date, despite a high prevalence of both individual infections, and thus likely also coinfections, in Mozambique. This aim plans to validate the initially suggested association of CHIKV infection and severe HIV-1 among CHIKV/HIV-1-coinfected patients. Furthermore, the functional reciprocal interplay of both pathogens at the level of cell-intrinsic innate immunity upon infection of monocyte-derived macrophages, a common target cell for both viruses, will be investigated by ex vivo experiments which will explore whether both viruses behave as friends or foes while multiplying in the identical cell.

• DFG Programme: Research Grants
• International Connection: Mozambique
• International Co-Applicant: Professor Dr. Eduardo Samo Gudo junior, Ph.D.