Armstrong Brittany A, Brandt Kevin S, Gilmore Robert D
Bacterial Diseases Branch, Division of Vector Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
Infect Immun. 2025 Apr 8;93(4):e0048424. doi: 10.1128/iai.00484-24. Epub 2025 Mar 7.
Relapsing fever (RFB) employs antigenic variation to alter its surface protein structure in response to host immune pressure. This process occurs by the single translocation of archived variable major protein (Vmp) pseudogenes into a expression locus. , phylogenetically grouped with RFB, has the genetic makeup for antigenic variation, but it has not been determined whether can create new variant serotypes . We inoculated mice with a non-clonal parental CT13-2396 strain with a known Vmp majority serotype with spirochete isolation at various days post-infection. The that determined the reisolated variant serotype was identified by PCR of the expression locus followed by DNA sequencing of the amplified product. For each mouse reisolate, new variants replaced the parent majority serotype. Moreover, some mice produced additional variant reisolates days apart, indicative of the presentation seen in relapsing fever infections. Infection of mice with a clonal population resulted in the elimination of the inoculated serotype and isolation of new variants. Mouse serum obtained following infection revealed IgM antibodies reactive to the parent Vmp serotype, suggesting that the immune response eliminated or greatly reduced the majority population. These results demonstrated that reisolated from infected mice exhibited serotype populations differing from the inoculated strain, indicating the spirochetes underwent antigenic variation to evade the host's immune response. However, whether the observed variation occurred by way of outgrowth of minority populations or by translocation of archived pseudogenes to the expression locus creating new variants awaits further study.
回归热(RFB)利用抗原变异来改变其表面蛋白结构,以应对宿主的免疫压力。这一过程通过将存档的可变主要蛋白(Vmp)假基因单一位点易位到一个表达位点来实现。,与回归热在系统发育上归为一组,具有抗原变异的基因组成,但尚未确定是否能产生新的变异血清型。我们用具有已知Vmp主要血清型的非克隆亲本CT13 - 2396菌株接种小鼠,并在感染后的不同天数进行螺旋体分离。通过对表达位点进行PCR,然后对扩增产物进行DNA测序,确定重新分离的变异血清型。对于每只小鼠重新分离株,新的变异株取代了亲本主要血清型。此外,一些小鼠在相隔数天产生了额外的变异重新分离株,这表明在回归热感染中出现的表现。用克隆群体感染小鼠导致接种血清型的消除和新变异株的分离。感染后获得的小鼠血清显示出对亲本Vmp血清型有反应的IgM抗体,这表明免疫反应消除或大大减少了主要群体。这些结果表明,从感染小鼠中重新分离的表现出血清型群体与接种菌株不同,表明螺旋体发生了抗原变异以逃避宿主的免疫反应。然而,观察到的变异是通过少数群体的生长还是通过存档假基因易位到表达位点产生新变异株的方式发生,还有待进一步研究。