Our data show that the target cells of SFFV largely mirror those of F-MuLV, with the highest virus loads in erythroblasts, B cells and myeloid cells. The early phase of infection was dominated by cells infected by either SFFV or F-MuLV, whereas double-infected cells became dominant later in the course of infection with increasing viral loads. In the late phase of infection, the frequency of double-infected cells was similarly high as the frequencies of SFFV or F-MuLV single-infected cells, and single- and double-infected cells outnumbered the uninfected cells in the most highly infected cell populations such as erythroblasts. FV and retroviruses in general have been shown to induce interleukin 10 (IL-10) as a means of suppressing immune responses. Interestingly, we found in infected IL-10-eGFP reporter mice that SFFV-infected cells contributed to the IL-10-producing cell pool much more significantly than F-MuLV-infected cells, suggesting that the truncated SFFV envelope protein gp55 might play a role in IL-10 induction. Even though BALB/c mice mount notoriously weak immune responses against FV, infection of mice with an ablation of IL-10 expression in T cells showed transiently lower viral loads and stronger T cell activation, suggesting that IL-10 induction by FV and by SFFV in particular may contribute to a suppressed immune response in BALB/c mice.
Our data provide detailed information about both F-MuLV- and SFFV-infected cells during the course of FV infection in highly susceptible mice and imply that the pathogenic SFFV contributes to immune suppression.
结果:我们的数据表明,SFFV的靶细胞在很大程度上反映了F-MuLV的靶细胞,成红细胞中病毒载量最高,B细胞和骨髓细胞。感染的早期阶段以SFFV或F-MuLV感染的细胞为主,而双重感染的细胞在感染过程中随着病毒载量的增加而变得占优势。在感染的晚期,双重感染细胞的频率与SFFV或F-MuLV单次感染细胞的频率相似,在高度感染的细胞群体中,单感染和双感染的细胞数量超过未感染的细胞,如成红细胞。FV和逆转录病毒通常已显示诱导白介素10(IL-10)作为抑制免疫应答的手段。有趣的是,我们在感染的IL-10-eGFP报告小鼠中发现,SFFV感染的细胞对产生IL-10的细胞池的贡献比F-MuLV感染的细胞显著得多,提示截短的SFFV包膜蛋白gp55可能在IL-10诱导中起作用。尽管BALB/c小鼠对FV的免疫反应非常弱,在T细胞中IL-10表达消融的小鼠感染显示出短暂降低的病毒载量和更强的T细胞活化,提示FV和特别是SFFV诱导的IL-10可能有助于抑制BALB/c小鼠的免疫应答。
结论:我们的数据提供了有关高度易感小鼠FV感染过程中F-MuLV和SFFV感染细胞的详细信息,并暗示致病性SFFV有助于免疫抑制。