Radical cure of HIV-1 (HIV) is hampered by the establishment of HIV reservoirs and persistent infection in deep tissues despite suppressive antiretroviral therapy (ART). Here, we show that among HIV-positive women receiving suppressive ART, cells from placental tissues including trophoblasts contain HIV RNA and DNA. These viruses can be reactivated by latency reversal agents. We find that syncytin, the envelope glycoprotein of human endogenous retrovirus family W1 expressed on placental trophoblasts, triggers cell fusion with HIV-infected T cells. This results in cell-to-cell spread of HIV to placental trophoblasts. Such cell-to-cell spread of HIV is less sensitive to ART than free virus. Replication in syncytin-expressing cells can also produce syncytin-pseudotyped HIV, further expanding its ability to infect non-CD4 cells. These previously unrecognized mechanisms of HIV entry enable the virus to bypass receptor restriction to infect host barrier cells, thereby facilitating viral transmission and persistent infection in deep tissues.

尽管建立了抗逆转录病毒疗法（ART），但由于建立了HIV储存库和深层组织持续感染，阻碍了HIV-1（HIV）的彻底治愈。在这里，我们表明，在接受抑制性ART的HIV阳性女性中，来自胎盘组织（包括滋养细胞）的细胞含有HIV RNA和DNA。这些病毒可以通过等待时间逆转代理重新激活。我们发现，合体素，在胎盘滋养细胞上表达的人类内源性逆转录病毒家族W1的包膜糖蛋白，触发了与HIV感染的T细胞的融合。这导致HIV在细胞间传播到胎盘滋养细胞。与游离病毒相比，这种HIV在细胞之间的传播对ART的敏感性较低。在表达合体素的细胞中复制还可以产生合体素假型的HIV，从而进一步扩大其感染非CD4细胞的能力。