Abstract：
Friend virus (FV) is a complex of the Friend murine leukemia virus (F-MuLV) and the replication-defective, pathogenic spleen focus forming virus (SFFV). In the past, we used a fluorescently labeled F-MuLV to analyze FV target cells. To build on these findings, we have now created a double-labeled FV that contains a Katushka-labeled F-MuLV and an mTagBFP-labeled SFFV, which we have used to study the infection by the two individual viruses in the FV infection of highly susceptible BALB/c mice.
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.
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.
摘要：
背景：Friend病毒（FV）是Friend鼠白血病病毒（F-MuLV）和复制缺陷的复合物，致病性脾斑形成病毒（SFFV）。在过去,我们使用荧光标记的F-MuLV分析FV靶细胞。在这些发现的基础上,我们现在已经创建了一个双标记的FV，它包含一个Katushka标记的F-MuLV和一个mTagBFP标记的SFFV，我们已用于研究两种个体病毒在高度易感的BALB/c小鼠的FV感染中的感染。
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。
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。
