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Impact des multiples infections naturelles par des rétrovirus simiens sur la charge provirale et la clonalité rétrovirale in vivo

Abstract : Non-human primates (NHPs) are natural hosts for exogenous retroviruses such as STLV-1 (Simian T-cell Leukemia Virus type 1) and SFV (Simian Foamy Virus), and natural cases of co-infections have been reported (SFV/STLV-1). As described for HTLV-1 in humans, STLV-1 is the etiologic agent of ATL (Adult T cell Leukemia) in NHPs, but the majority of infected animals remain asymptomatic. Furthermore, as for HTLV-1, which is able to replicate through clonal expansion of infected cells, the quantification of the proviral load together with the identification of proviral integration sites in STLV-1-infected NHPs have highlighted the clonal expansion of STLV-1 in vivo (Turpin et al., 2017). On the other hand, SFV is considered as non-pathogenic, but whether co-infections might regulate SFV replication is unknown. The aim of the project is to evaluate the influence of STLV-1 on the proviral load and the retroviral clonality of SFV in naturally infected baboons. First, we have reported that the SFV proviral load increases in the blood of baboons naturally co-infected with SFV and STLV-1 (Alais et al., 2018). We next demonstrate for the first time that SFV is able to replicate by clonal expansion of infected cells in vivo, as described for HTLV-1 and STLV-1. However, STLV-1 does not seem to promote clonal expansion of SFV in vivo. Lastly, in order to analyze if one unique cell can be co-infected by both SFV and STLV-1 in vivo, we develop a DNA-FISH (fluorescence in situ hybridization) approach. Altogether, this work sheds light on the replication of SFV in naturally infected NHPs, and emphasizes the fact that co-infection can significantly impact the replication of exogenous viruses in vivo
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Submitted on : Friday, September 24, 2021 - 9:19:51 AM
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Brice Jegado. Impact des multiples infections naturelles par des rétrovirus simiens sur la charge provirale et la clonalité rétrovirale in vivo. Maladies infectieuses. Université de Lyon, 2020. Français. ⟨NNT : 2020LYSE1272⟩. ⟨tel-03353420⟩

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