Defining early SIV replication and dissemination dynamics following vaginal transmission
Defining early SIV replication and dissemination dynamics following vaginal transmission
复制标题
DOI：
10.1126/sciadv.aav7116
复制
发表时间：
2019-05-01
期刊：
影响因子：
13.6
通讯作者：
Keele, Brandon F.
中科院分区：
文献类型：
--
作者：
Deleage, Claire;Immonen, Taina T.;Keele, Brandon F.
了解艾滋病毒传播对于指导制定预防感染的预防性干预措施至关重要。我们使用非人灵长类动物 (NHP) 模型，该模型具有 SIVmac239 (“SIVmac239X”) 序列标记变体的合成群，并在初次感染期间（攻击后第 3 至 14 天）进行预定尸检，以研究病毒动力学和宿主对阴道攻击后感染建立和传播的反应。我们证明局部复制是在女性生殖道（FGT）内的多个位点启动的，每个位点都有多种病毒变体。 FGT 中的局部复制和扩散先于淋巴传播。观察到先天病毒限制因子，但似乎遵循病毒复制，并且不能有效阻止病毒最初的建立和传播。然而，在动物中以及同一动物内不同病毒变体之间的传播时间出现了重大延迟。评估表型差异如何影响早期病毒动力学非常重要。
Understanding HIV transmission is critical to guide the development of prophylactic interventions to prevent infection. We used a nonhuman primate (NHP) model with a synthetic swarm of sequence-tagged variants of SIVmac239 ("SIVmac239X") and scheduled necropsy during primary infection (days 3 to 14 after challenge) to study viral dynamics and host responses to the establishment and dissemination of infection following vaginal challenge. We demonstrate that local replication was initiated at multiple sites within the female genital tract (FGT), with each site having multiple viral variants. Local replication and spread in the FGT preceded lymphatic dissemination. Innate viral restriction factors were observed but appeared to follow viral replication and were ineffective at blocking initial viral establishment and dissemination. However, major delays were observed in time to dissemination in animals and among different viral variants within the same animal. It will be important to assess how phenotypic differences affect early viral dynamics.