The existence of multiple subtypes of Human immunodeficiency virus (HIV), its rapid evolution and the presence of an error-prone reverse transcriptase enzyme with highly recombinogenic activity render particularly difficult the search for a unique cure for all HIV-infected individuals. Distinct HIV clades have shown striking differences in respect to infection course, progression to AIDS and response to therapy. Therefore, it is crucial to better characterize distinct HIV subtypes in respect to virus-host interactions. Indeed, out knowledge of inter-subtypes differences of viral pathogenic mechanisms and immune correlates of protection are still very poor and limited to few studies, that anyway suggest that proteins from distinct HIV clades may differently contribute to immune dysfunctions.
This project builds on the previous expertise developed by the applicants in study of HIV immunity, pathogenesis and epidemiology. The 4 participants (Francesco Nicoli, University of Ferrara, Italy; Mkunde Chachage, Mbeya Medical Research Center, Tanzania; Deepak Paudel, Save the Children, Nepal; María Teresa Solis Soto, San Francisco Xavier de Chuquisaca University, Bolivia) integrated orthogonal approaches spanning from immunology to public health, to shed light on HIV inter clades differences in respect to: i) virus-host interactions and ii) correlates of protections.
They characterized several properties of the HIV-1 Tat protein on CD4+ and CD8+ T-cells, identifying clade-related differences. In summary, clade B and C Tat have opposite effects on quiescent lymphocytes. Analyzing cytokine secretion, transcription factor expression and metabolic properties (by both flow cytometry and qPCR), they observed that clade B Tat is keeping and ensuring the quiescent of resting T-cells, while clade C Tat not. A further set of experiments we preformed was aimed at investigating the degradation of Tat by the proteasome. This work was possible also through the collaboration with other institution, such the ISS in Rome and the CIMI-Paris in France and the set up and participation to several training courses.
Part of the work performed will be soon published. The rest will serve as basis for the future projects we plan to develop.