Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission
Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission
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早期 SIV 直肠传播组织中代表性不均的始祖病毒的鉴定。
DOI：
10.3389/fmicb.2018.00557
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发表时间：
2018-03-29
影响因子：
5.2
通讯作者：
Xu, Jianqing
中科院分区：
文献类型：
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作者：
Chen, Jian;Ren, Yanqin;Xu, Jianqing
表征多变异SIV感染的传播/创始者（T/F）病毒可能为理解粘膜传播提供新的思路。我们用单次高剂量的SIVmac 251（3.1 × 10（4）TCID 50）直肠内接种6只中国恒河猴，并在感染后6天和10天通过单基因组扩增（SGA）从多个组织中获得985个全长env序列。所有6只猴均感染了2 - 8种T/F病毒，接种物的显性变体在每只猴的不同组织中仍占优势。有趣的是，我们的数据显示，一组罕见的T/F病毒在不同组织中的代表性不相等。这组罕见的T/F病毒与接种物中的非显性SIV变体在遗传学上相关，在任何直肠组织中均未检出，但可在降结肠、空肠、脾脏或血浆中检出。在6只猕猴中的2只中，在降结肠/空肠和接种物中同时检测到属于该簇的相同SIVmac 251变体。我们还证明，这些罕见的T/F病毒在组织中发现的平均CG二核苷酸频率，以及接种物中的非显性变体，显着高于显性T/F病毒在组织和接种物。总的来说，这些研究结果表明，降结肠/空肠可能比直肠更容易感染SIV在非常早期的阶段。而宿主CG抑制，这是以前被证明可以抑制HIV在体外复制，也可能有助于在体内传播过程中的瓶颈选择。
Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 x 10(4) TCID50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses was unequally represented in different tissues. This cluster of rare T/F viruses phylogenetically related to the non-dominant SIV variants in the inoculum and was not detected in any rectum tissues, but could be identified in the descending colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251 variants belonging to this cluster were detected simultaneously in descending colon/jejunum and the inoculum. We also demonstrated that the average CG dinucleotide frequency of these rare T/F viruses found in tissues, as well as non-dominant variants in the inoculum, was significantly higher than the dominant T/F viruses in tissues and the inoculum. Collectively, these findings suggest that descending colon/jejunum might be more susceptible than rectum to SIV in the very early phase of infection. And host CG suppression, which was previously shown to inhibit HIV replication in vitro, may also contribute to the bottleneck selection during in vivo transmission.