Clonal expansion of SFV infected cells in Papio anubis. Retroviral clonality

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 and mechanisms involved in co-infections to 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. Our study also shows that SFV proviruses preferentially integrate within repeated regions in the baboon's genome. Moreover, STLV-1 does not seem to promote the propagation of SFV in vivo. Altogether, this work sheds light on the replication of SFV in naturally infected NHPs, and emphasizes the fact that co-infection with STLV-1 has no impact on SFV replication in vivo.

非人灵长类（Non-human primates, NHPs）是STLV-1（猴T细胞白血病病毒1型，Simian T-cell Leukemia Virus type 1）、SFV（猴泡沫病毒，Simian Foamy Virus）等外源性逆转录病毒的天然宿主，已有研究报道了二者共感染（SFV/STLV-1）的自然病例。正如人类HTLV-1（人类T细胞白血病病毒1型，Human T-cell Leukemia Virus type 1）的相关研究所述，STLV-1是非人灵长类罹患ATL（成人T细胞白血病，Adult T cell Leukemia）的致病因子，但大多数感染动物并无临床症状。进一步而言，与HTLV-1类似，STLV-1可通过感染细胞的克隆扩增实现复制；对感染STLV-1的非人灵长类的前病毒载量定量及前病毒整合位点的鉴定研究，已证实STLV-1在体内存在克隆扩增现象（Turpin等人，2017）。与之相对，SFV被认为无致病性，且目前调控SFV复制的共感染机制仍不明晰。本项目旨在评估STLV-1对自然感染狒狒体内SFV的前病毒载量及逆转录病毒克隆性的影响。首先，本团队已报道自然共感染SFV与STLV-1的狒狒血液中SFV前病毒载量升高的现象（Alais等人，2018）。本研究首次证实，SFV可如HTLV-1与STLV-1所述，通过感染细胞的克隆扩增在体内实现复制。本研究还发现，SFV前病毒优先整合至狒狒基因组的重复序列区域。此外，STLV-1似乎并未促进SFV在体内的增殖。综上，本研究阐明了SFV在自然感染非人灵长类体内的复制机制，并证实STLV-1共感染对SFV的体内复制并无影响。