School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
Child Health Research Center, University of Queensland, South Brisbane, Australia.
PLoS Pathog. 2018 Feb 15;14(2):e1006905. doi: 10.1371/journal.ppat.1006905. eCollection 2018 Feb.
Cytomegaloviruses (CMVs) persistently and systemically infect the myeloid cells of immunocompetent hosts. Persistence implies immune evasion, and CMVs evade CD8+ T cells by inhibiting MHC class I-restricted antigen presentation. Myeloid cells can also interact with CD4+ T cells via MHC class II (MHC II). Human CMV (HCMV) attacks the MHC II presentation pathway in vitro, but what role this evasion might play in host colonization is unknown. We show that Murine CMV (MCMV) down-regulates MHC II via M78, a multi-membrane spanning viral protein that captured MHC II from the cell surface and was necessary although not sufficient for its degradation in low pH endosomes. M78-deficient MCMV down-regulated MHC I but not MHC II. After intranasal inoculation, it showed a severe defect in salivary gland colonization that was associated with increased MHC II expression on infected cells, and was significantly rescued by CD4+ T cell loss. Therefore MCMV requires CD4+ T cell evasion by M78 to colonize the salivary glands, its main site of long-term shedding.
巨细胞病毒（CMV）持续且系统性地感染免疫功能正常宿主的髓系细胞。持续性意味着免疫逃避，CMV 通过抑制 MHC Ⅰ类限制的抗原呈递来逃避 CD8+T 细胞。髓系细胞还可以通过 MHC Ⅱ（MHC II）与 CD4+T 细胞相互作用。人巨细胞病毒（HCMV）在体外攻击 MHC II 呈递途径，但这种逃避在宿主定植中可能起什么作用尚不清楚。我们发现鼠巨细胞病毒（MCMV）通过 M78 下调 MHC II，M78 是一种具有多个跨膜区的病毒蛋白，可从细胞表面捕获 MHC II，并在低 pH 内体中进行降解是必需的，但不是充分的。M78 缺陷型 MCMV 下调 MHC I，但不下调 MHC II。经鼻腔接种后，其在唾液腺定植中出现严重缺陷，与感染细胞上 MHC II 表达增加有关，而 CD4+T 细胞缺失可显著挽救这一缺陷。因此，MCMV 通过 M78 逃避 CD4+T 细胞来定植唾液腺，这是其长期脱落的主要部位。
