Krejbich-Trotot Pascale, Belarbi Essia, Ralambondrainy Miora, El-Kalamouni Chaker, Viranaicken Wildriss, Roques Pierre, Desprès Philippe, Gadea Gilles
UM 134 Processus Infectieux en Milieu Insulaire Tropical (PIMIT), INSERM U1187, CNRS UMR9192, IRD UMR249, Université de la Réunion, Plateforme Technologique CYROI, 97490 Sainte Clotilde, La Réunion, France.
CEA, Division of Immuno-Virologie, Institute of Emerging Diseases and Innovative Therapies, INSERM, U1184, Fontenay-aux-Roses, France; Pasteur Institute, Environment and Infectious Risks unit, 75015 Paris, France.
Virus Res. 2016 Oct 2;225:64-68. doi: 10.1016/j.virusres.2016.09.007. Epub 2016 Sep 13.
Alphaviruses such as Chikungunya and Ross River (RRV) viruses are associated with persistent arthritis and arthralgia in humans. Monocytes and macrophages are believed to play an important role in alphaviral arthritides. In this study, we evaluated RRV permissiveness of the human acute leukemia MM6 cell line. Viral growth analysis showed that RRV infection of MM6 cells resulted in a very low virus progeny production with daily output. Using recombinant RRV expressing the reporter gene Renilla luciferase, a weak viral replication level was detected in infected cells at the early stages of infection. The infection restriction was not associated with type-I interferon and pro-inflammatory cytokines release. Apoptosis hallmarks (i.e. mitochondrial BAX localisation and PARP cleavage) were observed in infected MM6 cells indicating that RRV can trigger apoptosis at late infection times. The long-term persistence of RRV genomic RNA in surviving MM6 cells identifies human monocytic cells as potential cellular reservoirs of viral material within the infected host.
诸如基孔肯雅病毒和罗斯河病毒(RRV)等甲病毒与人类持续性关节炎和关节痛有关。单核细胞和巨噬细胞被认为在甲病毒关节炎中起重要作用。在本研究中,我们评估了人急性白血病MM6细胞系对RRV的易感性。病毒生长分析表明,RRV感染MM6细胞导致每日病毒子代产量非常低。使用表达报告基因海肾荧光素酶的重组RRV,在感染早期在感染细胞中检测到较弱的病毒复制水平。感染限制与I型干扰素和促炎细胞因子的释放无关。在感染的MM6细胞中观察到凋亡特征(即线粒体BAX定位和PARP裂解),表明RRV可在感染后期触发凋亡。RRV基因组RNA在存活的MM6细胞中的长期持续存在表明人单核细胞是感染宿主内病毒物质的潜在细胞储存库。