性染色体组成对柯萨奇病毒 B3 但不对甲型流感病毒发病机制的性别差异有贡献。
Sex chromosome complement contributes to sex differences in coxsackievirus B3 but not influenza A virus pathogenesis.
机构信息
The W Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
出版信息
Biol Sex Differ. 2011 Aug 1;2:8. doi: 10.1186/2042-6410-2-8.
BACKGROUND
Both coxsackievirus B3 (CVB3) and influenza A virus (IAV; H1N1) produce sexually dimorphic infections in C57BL/6 mice. Gonadal steroids can modulate sex differences in response to both viruses. Here, the effect of sex chromosomal complement in response to viral infection was evaluated using four core genotypes (FCG) mice, where the Sry gene is deleted from the Y chromosome, and in some mice is inserted into an autosomal chromosome. This results in four genotypes: XX or XY gonadal females (XXF and XYF), and XX or XY gonadal males (XXM and XYM). The FCG model permits evaluation of the impact of the sex chromosome complement independent of the gonadal phenotype.
METHODS
Wild-type (WT) male and female C57BL/6 mice were assigned to remain intact or be gonadectomized (Gdx) and all FCG mice on a C57BL/6 background were Gdx. Mice were infected with either CVB3 or mouse-adapted IAV, A/Puerto Rico/8/1934 (PR8), and monitored for changes in immunity, virus titers, morbidity, or mortality.
RESULTS
In CVB3 infection, mortality was increased in WT males compared to females and males developed more severe cardiac inflammation. Gonadectomy suppressed male, but increased female, susceptibility to CVB3. Infection with IAV resulted in greater morbidity and mortality in WT females compared with males and this sex difference was significantly reduced by gonadectomy of male and female mice. In Gdx FCG mice infected with CVB3, XY mice were less susceptible than XX mice. Protection correlated with increased CD4+ forkhead box P3 (FoxP3)+ T regulatory (Treg) cell activation in these animals. Neither CD4+ interferon (IFN)γ (T helper 1 (Th1)) nor CD4+ interleukin (IL)-4+ (Th2) responses differed among the FCG mice during CVB3 infection. Infection of Gdx FCG mice revealed no effect of sex chromosome complement on morbidity or mortality following IAV infection.
CONCLUSIONS
These studies indicate that sex chromosome complement can influence pathogenicity of some, but not all, viruses.
背景
柯萨奇病毒 B3（CVB3）和甲型流感病毒（IAV；H1N1）在 C57BL/6 小鼠中产生性别二态性感染。性腺类固醇可以调节对这两种病毒的性别差异反应。在这里，使用四个核心基因型（FCG）小鼠评估了性染色体组成对病毒感染的影响，其中 Sry 基因从 Y 染色体缺失，并在一些小鼠中插入常染色体。这导致了四种基因型：XX 或 XY 性腺雌性（XXF 和 XYF），以及 XX 或 XY 性腺雄性（XXM 和 XYM）。FCG 模型允许在不考虑性腺表型的情况下评估性染色体组成的影响。
方法
将野生型（WT）雄性和雌性 C57BL/6 小鼠分配为保持完整或去势（Gdx），并且所有 C57BL/6 背景的 FCG 小鼠均进行 Gdx。用 CVB3 或适应小鼠的流感病毒 A/Puerto Rico/8/1934（PR8）感染小鼠，并监测免疫、病毒滴度、发病率或死亡率的变化。
结果
在 CVB3 感染中，与雌性相比，WT 雄性的死亡率增加，雄性心脏炎症更严重。去势抑制了雄性，但增加了雌性对 CVB3 的易感性。与雄性相比，IAV 感染导致 WT 雌性的发病率和死亡率更高，而雄性和雌性小鼠的去势显著降低了这种性别差异。在感染 CVB3 的 Gdx FCG 小鼠中，XY 小鼠比 XX 小鼠更不易受感染。在这些动物中，保护与增加 CD4+叉头框 P3（FoxP3）+调节性 T 细胞（Treg）的激活相关。在 CVB3 感染期间，FCG 小鼠的 CD4+干扰素（IFN）γ（Th1）和 CD4+白细胞介素（IL）-4+（Th2）反应均无差异。感染 Gdx FCG 小鼠表明，性染色体组成对 IAV 感染后的发病率或死亡率没有影响。
结论
这些研究表明，性染色体组成可以影响某些，但不是所有病毒的致病性。
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