T cell deficiency precipitates antibody evasion and emergence of neurovirulent polyomavirus.
T cell deficiency precipitates antibody evasion and emergence of neurovirulent polyomavirus.
复制标题
T细胞缺乏会沉淀出抗体逃避和神经性多瘤病毒的出现。
DOI：
10.7554/elife.83030
复制
发表时间：
2022-11-07
期刊：
影响因子：
7.7
通讯作者：
Lukacher AE
中科院分区：
文献类型：
--
作者：
Lauver MD;Jin G;Ayers KN;Carey SN;Specht CS;Abendroth CS;Lukacher AE
JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease in immunocompromised patients. Inherited and acquired T cell deficiencies are associated with PML. The incidence of PML is increasing with the introduction of new immunomodulatory agents, several of which target T cells or B cells. PML patients often carry mutations in the JCPyV VP1 capsid protein, which confer resistance to neutralizing VP1 antibodies (Ab). Polyomaviruses (PyV) are tightly species-specific; the absence of tractable animal models has handicapped understanding PyV pathogenesis. Using mouse polyomavirus (MuPyV), we found that T cell deficiency during persistent infection, in the setting of monospecific VP1 Ab, was required for outgrowth of VP1 Ab-escape viral variants. CD4 T cells were primarily responsible for limiting polyomavirus infection in the kidney, a major reservoir of persistent infection by both JCPyV and MuPyV, and checking emergence of these mutant viruses. T cells also provided a second line of defense by controlling the outgrowth of VP1 mutant viruses that evaded Ab neutralization. A virus with two capsid mutations, one conferring Ab-escape yet impaired infectivity and a second compensatory mutation, yielded a highly neurovirulent variant. These findings link T cell deficiency and evolution of Ab-escape polyomavirus VP1 variants with neuropathogenicity.
