A little cooperation helps murine cytomegalovirus (MCMV) go a long way: MCMV co-infection rescues a chemokine salivary gland defect.
A little cooperation helps murine cytomegalovirus (MCMV) go a long way: MCMV co-infection rescues a chemokine salivary gland defect.
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一点点合作有助于鼠巨细胞病毒 (MCMV) 取得长足进步：MCMV 共同感染可挽救趋化因子唾液腺缺陷。
DOI：
10.1099/jgv.0.000603
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Sparer,Tim
中科院分区：
文献类型：
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作者：
Dogra,Pranay;Miller-Kittrell,Mindy;Pitt,Elisabeth;Jackson,JosephW;Masi,Tom;Copeland,Courtney;Wu,Shuen;Miller,WilliamE;Sparer,Tim
巨细胞病毒（CMV）产生与宿主趋化因子具有序列和功能同源性的趋化因子（vCXCL）。由于CMV的种属特异性，vCXCL-1在CMV感染中的作用的评估仅限于体外和计算机分析。在本研究中，我们使用小鼠巨细胞病毒（MCMV）小鼠模型来评估vCXCL-1在体内的功能。表达黑猩猩CMV vCXCL-1（vCXCL-1CCMV）或宿主趋化因子mCXCL 1的重组MCMV与亲本MCMV相似，主要播散至腘淋巴结、脾和肺。然而，表达趋化因子的重组体在感染后的任何时间都没有从唾液腺（SG）中回收，尽管检测到病毒DNA。这意味着病毒不在SG中生长，或者过表达的趋化因子诱导导致生长抑制的免疫应答。针对病毒复制的免疫抑制，在免疫消除小鼠感染后从SG分离重组病毒[即，SCID（严重联合免疫缺陷）、NSG（非肥胖糖尿病SCID γ）或环磷酰胺治疗]。中性粒细胞或NK细胞的消耗并不能挽救SG中表达趋化因子的重组体的恢复。令人惊讶的是，我们发现亲本病毒和表达趋化因子的病毒的共感染导致SG中重组体的恢复。我们认为亲代病毒降低了趋化因子的表达水平，导致炎性单核细胞和随后的SG生长减少。因此，趋化因子的异常表达诱导先天性和适应性免疫系统的细胞，其减少重组体在SG中的生长和传播。
Cytomegaloviruses (CMVs) produce chemokines (vCXCLs) that have both sequence and functional homology to host chemokines. Assessment of vCXCL-1's role in CMV infection is limited toin vitroandin silicoanalysis due to CMVs species specificity. In this study, we used the murine CMV (MCMV) mouse model to evaluate the function of vCXCL-1in vivo. Recombinant MCMVs expressing chimpanzee CMV vCXCL-1 (vCXCL-1CCMV) or host chemokine, mCXCL1, underwent primary dissemination to the popliteal lymph node, spleen and lung similar to the parental MCMV. However, neither of the recombinants expressing chemokines was recovered from the salivary gland (SG) at any time post-infection although viral DNA was detected. This implies that the virus does not grow in the SG or the overexpressed chemokine induces an immune response that leads to suppressed growth. Pointing to immune suppression of virus replication, recombinant viruses were isolated from the SG following infection of immune-ablated mice [i.e. SCID (severe combined immunodeficiency), NSG (non-obese diabetic SCID gamma) or cyclophosphamide treated]. Depletion of neutrophils or NK cells does not rescue the recovery of chemokine-expressing recombinants in the SG. Surprisingly we found that co-infection of parental virus and chemokine-expressing virus leads to the recovery of the recombinants in the SG. We suggest that parental virus reduces the levels of chemokine expression leading to a decrease in inflammatory monocytes and subsequent SG growth. Therefore, aberrant expression of the chemokines induces cells of the innate and adaptive immune system that curtail the growth and dissemination of the recombinants in the SG.