Cell-free human immunodeficiency virus type 1 transcytosis through primary genital epithelial cells
Cell-free human immunodeficiency virus type 1 transcytosis through primary genital epithelial cells
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DOI：
10.1128/jvi.01303-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Gallay, Philippe A.
中科院分区：
文献类型：
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作者：
Bobardt, Michael D.;Chatterji, Udayan;Gallay, Philippe A.
虽然人类免疫缺陷病毒1型（HIV-1）通过上皮细胞的运输是HIV-1定植的关键，控制这一过程的机制仍然不清楚。在本研究中，我们研究了HIV-1作为一种无细胞病毒通过原代生殖器上皮细胞（PGECs）的跨细胞迁移。PGEC上CD 4的缺失暗示了HIV-1的不寻常的进入途径。我们发现多配体蛋白聚糖在PGEC上大量表达，并促进HIV-1通过PGEC的初始附着和随后的进入。尽管CXCR 4和CCR 5不参与HIV-1附着，但它们通过PGEC增强病毒进入和转胞吞作用。重要的是，HIV-1利用多配体蛋白聚糖和趋化因子受体来确保成功的无细胞转运通过生殖器上皮。HIV-1-多配体蛋白聚糖相互作用依赖于gp 120的V3中的特定残基和多配体蛋白聚糖内的特定硫酸化。我们发现辅助受体的使用和病毒转胞吞的能力之间没有明显的相关性。由于性传播后分离的病毒主要是R5病毒，这表明传播后赋予病毒复制的性质与赋予无细胞病毒通过生殖器上皮转胞吞的性质不同。虽然我们发现无细胞HIV-1作为感染性颗粒穿过PGEC，但转胞吞作用的效率极低（低于初始接种物的0.02%）。这表明生殖器上皮是抵抗HIV-1的主要屏障。尽管不能排除无细胞HIV-1转胞吞作用在体内通过完整生殖器上皮有限通过的可能性，但通过无细胞HIV-1转胞吞作用建立感染很可能是罕见事件。
Although the transport of human immunodeficiency virus type 1 (HIV-1) through the epithelium is critical for HIV-1 colonization, the mechanisms controlling this process remain obscure. In the present study, we investigated the transcellular migration of HIV-1 as a cell-free virus through primary genital epithelial cells (PGECs). The absence of CD4 on PGECs implicates an unusual entry pathway for HIV-1. We found that syndecans are abundantly expressed on PGECs and promote the initial attachment and subsequent entry of HIV-1 through PGECs. Although CXCR4 and CCR5 do not contribute to HIV-1 attachment, they enhance viral entry and transcytosis through PGECs. Importantly, HIV-1 exploits both syndecans and chemokine receptors to ensure successful cell-free transport through the genital epithelium. HIV-1-syndecan interactions rely on specific residues in the V3 of gp120 and specific sulfations within syndecans. We found no obvious correlation between coreceptor usage and the capacity of the virus to transcytose. Since viruses isolated after sexual transmission are mainly R5 viruses, this suggests that the properties conferring virus replication after transmission are distinct from those conferring cell-free virus transcytosis through the genital epithelium. Although we found that cell-free HIV-1 crosses PGECs as infectious particles, the efficiency of transcytosis is extremely poor (less than 0.02% of the initial inoculum). This demonstrates that the genital epithelium serves as a major barrier against HIV-1. Although one cannot exclude the possibility that limited passage of cell-free HIV-1 transcytosis through an intact genital epithelium occurs in vivo, it is likely that the establishment of infection via cell-free HIV-1 transmigration is a rare event.