Serotype-Specific Host Responses in Rhesus Macaques after Primary Dengue Challenge
Serotype-Specific Host Responses in Rhesus Macaques after Primary Dengue Challenge
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DOI：
10.4269/ajtmh.13-0145
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发表时间：
2013-12-01
影响因子：
3.3
通讯作者：
Bossart, Katharine N.
中科院分区：
文献类型：
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作者：
Hickey, Andrew C.;Koster, Jacob A.;Bossart, Katharine N.
登革病毒（DENV）被认为是最重要的节肢动物传播的病毒性疾病，每年导致超过1亿人感染。为了进一步表征体内原发性DENY感染，用DENV-1、DENV-2、DENV-3或DENV-4感染恒河猴，并评估临床参数以及血清学应答的特异性和寿命。感染后无明显临床症状。然而，观察到与心脏、肾脏和肝脏损伤一致的血液生化参数异常，血浆纤维蛋白原、D-二聚体和蛋白C的变化表明凝血途径的全身激活。所有动物中均存在显著的同型和异型血清免疫球蛋白，IgG持续至少390天。到第120天，血清中和抗体应答具有高度血清型特异性。然而，在感染动物中观察到一些异型中和活性。鉴定病毒型特异性宿主反应可能有助于阐明再感染后介导严重DENY疾病的机制。
Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENY infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENY disease after reinfection.