HIV-1 Productively Infects and Integrates in Bronchial Epithelial Cells.
HIV-1 Productively Infects and Integrates in Bronchial Epithelial Cells.
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DOI：
10.3389/fcimb.2020.612360
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发表时间：
2020
影响因子：
5.7
通讯作者：
Sopori M
中科院分区：
文献类型：
--
作者：
Devadoss D;Singh SP;Acharya A;Do KC;Periyasamy P;Manevski M;Mishra N;Tellez CS;Ramakrishnan S;Belinsky SA;Byrareddy SN;Buch S;Chand HS;Sopori M
肺上皮细胞在HIV-1相关性肺部合并症中的作用尚不清楚，治愈HIV的主要障碍是HIV携带者(PLWH)中潜伏的HIV宿主的持久性。联合抗逆转录病毒治疗的出现大大延长了寿命；然而，慢性肺部疾病在PLWH中的发病率明显更高。肺上皮细胞协调呼吸道免疫反应，这些细胞是否有效地感染了HIV-1尚有争议。用X4嗜性HIV-1LAV感染生长在气液界面上的正常人支气管上皮细胞(NHBE)，并用潜伏期反转剂(LRA)检测潜伏期。检测CD4和CXCR4共受体在NHBE中的作用，并用DNA测序分析HIV前病毒基因Alu-HIVgag-Poll、HIV-nef和HIV-Ltr的基因组整合。用FISH技术对HIV感染者和SHIV感染者的肺上皮切片进行HIV-Gag-PolRNA和上皮细胞特异性免疫染色。与A549细胞相比，NHBE细胞高表达CD4和CXCR4。NHBE可被X4嗜性HIV-1LAV以CXCR4/CD4依赖的方式感染HIV-1，导致HIV-p24抗原的产生；然而，IL-13诱导NHBE表达CCR5。在CART存在的情况下，HIV-1诱导HIV前病毒在细胞DNA中的潜伏和整合，这是由LRAS(内毒素/涡旋化器)拯救的。此外，来自HIV感染者和Shiv感染猕猴的肺上皮细胞含有HIV特异的RNA转录本。因此，肺上皮细胞是HIV-1的靶点，并可能成为潜在的HIV宿主，可能导致PLWH的呼吸道共病。
The role of lung epithelial cells in HIV-1-related lung comorbidities remains unclear, and the major hurdle in curing HIV is the persistence of latent HIV reservoirs in people living with HIV (PLWH). The advent of combined antiretroviral therapy has considerably increased the life span; however, the incidence of chronic lung diseases is significantly higher among PLWH. Lung epithelial cells orchestrate the respiratory immune responses and whether these cells are productively infected by HIV-1 is debatable. Normal human bronchial epithelial cells (NHBEs) grown on air–liquid interface were infected with X4-tropic HIV-1LAV and examined for latency using latency-reversing agents (LRAs). The role of CD4 and CXCR4 HIV coreceptors in NHBEs were tested, and DNA sequencing analysis was used to analyze the genomic integration of HIV proviral genes, Alu-HIVgag-pol, HIV-nef, and HIV-LTR. Lung epithelial sections from HIV-infected humans and SHIV-infected macaques were analyzed by FISH for HIV-gag-pol RNA and epithelial cell-specific immunostaining. NHBEs express CD4 and CXCR4 at higher levels than A549 cells. NHBEs are infected with HIV-1 basolaterally, but not apically, by X4-tropic HIV-1LAV in a CXCR4/CD4-dependent manner leading to HIV-p24 antigen production; however, NHBEs are induced to express CCR5 by IL-13 treatment. In the presence of cART, HIV-1 induces latency and integration of HIV provirus in the cellular DNA, which is rescued by the LRAs (endotoxin/vorinostat). Furthermore, lung epithelial cells from HIV-infected humans and SHIV-infected macaques contain HIV-specific RNA transcripts. Thus, lung epithelial cells are targeted by HIV-1 and could serve as potential HIV reservoirs that may contribute to the respiratory comorbidities in PLWH.
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影响因子：
10.5
作者：
Dahabieh MS;Battivelli E;Verdin E
通讯作者：
Verdin E
影响因子：
24.3
作者：
Maitre, Thomas;Cottenet, Jonathan;Quantin, Catherine
通讯作者：
Quantin, Catherine
影响因子：
8.8
作者：
Ferrer, P.;Tello, M.;Afani, A.
通讯作者：
Afani, A.
DOI：
10.1097/qad.0000000000001962
发表时间：
2018-10-23
期刊：
AIDS (London, England)
影响因子：
--
作者：
Costiniuk CT;Salahuddin S;Farnos O;Olivenstein R;Pagliuzza A;Orlova M;Schurr E;De Castro C;Bourbeau J;Routy JP;Ancuta P;Chomont N;Jenabian MA
通讯作者：
Jenabian MA
内包皮组织和外包皮组织中 HIV 靶向免疫细胞的差异区室化
影响因子：
3.7
作者：
Liu A;Yang Y;Liu L;Meng Z;Li L;Qiu C;Xu J;Zhang X
通讯作者：
Zhang X