AP-HP, Hôpital Henri Mondor, Service d'Immunologie et Maladies Infectieuses, Université Paris Est Créteil, Inserm U955, Créteil, France.
AP-HP, Hôpital Saint-Louis, Virologie, Paris, France.
Sci Rep. 2020 Feb 12;10(1):2409. doi: 10.1038/s41598-020-59234-6.
We used next-generation sequencing to evaluate the quantity and genetic diversity of the HIV envelope gene in various compartments in eight patients with acute infection. Plasma (PL) and seminal fluid (SF) were available for all patients, whole blood (WB) for seven, non-spermatozoid cells (NSC) for four, and saliva (SAL) for three. Median HIV-1 RNA was 6.2 log copies/mL [IQR: 5.5-6.95] in PL, 4.9 log copies/mL [IQR: 4.25-5.29] in SF, and 4.9 log copies/mL [IQR: 4.46-5.09] in SAL. Median HIV-1 DNA was 4.1 log copies/10 PBMCs [IQR: 3.15-4.15] in WB and 2.6 log copies /10 Cells [IQR: 2.23-2.75] in NSC. The median overall diversity per patient varied from 0.0005 to 0.0232, suggesting very low diversity, confirmed by the clonal aspect of most of the phylogenetic trees. One single haplotype was present in all compartments for five patients in the earliest stage of infection. Evidence of higher diversity was established for two patients in PL and WB, suggesting compartmentalization. Our study shows low diversity of the env gene in the first stages of infection followed by the rapid establishment of cellular reservoirs of the virus. Such clonality could be exploited in the search for early patient-specific therapeutic solutions.
我们使用下一代测序技术来评估 8 名急性感染患者不同部位 HIV 包膜基因的数量和遗传多样性。所有患者均有血浆（PL）和精液（SF）样本，7 名患者有全血（WB）样本，4 名患者有非精子细胞（NSC）样本，3 名患者有唾液（SAL）样本。PL 中 HIV-1 RNA 的中位数为 6.2 log 拷贝/mL [IQR：5.5-6.95]，SF 中为 4.9 log 拷贝/mL [IQR：4.25-5.29]，SAL 中为 4.9 log 拷贝/mL [IQR：4.46-5.09]。WB 中 HIV-1 DNA 的中位数为 4.1 log 拷贝/10 PBMCs [IQR：3.15-4.15]，NSC 中为 2.6 log 拷贝/10 细胞 [IQR：2.23-2.75]。每位患者的总体多样性中位数从 0.0005 到 0.0232 不等，表明多样性非常低，大多数系统发育树的克隆特征也证实了这一点。在感染的最早阶段，有 5 名患者的所有部位均存在单一单倍型。在 PL 和 WB 中，有 2 名患者的多样性证据更高，提示存在隔室化。我们的研究表明，在感染的早期阶段，env 基因的多样性很低，随后病毒的细胞储库迅速建立。这种克隆性可以用于寻找早期患者特异性治疗方法。
