| 1. |
- Chen, Jian, et al.
(författare)
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Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects
- 2017
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Ingår i: Emerging Microbes & Infections. - : NATURE PUBLISHING GROUP. - 2222-1751. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain-Barre syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients' urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients' urine.
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| 2. |
- Chen, Jian, et al.
(författare)
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AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling
- 2018
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 3:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barre syndrome(1,2). While progress has been made in understanding the causal link between ZIKV infection and microcephaly(3-9), the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role of AXL, a TAM family kinase receptor that was initially described as the entry receptor for ZIKV(10-22). Here, we show that while genetic ablation of AXL protected primary human astrocytes and astrocytoma cell lines from ZIKV infection, AXL knockout did not block the entry of ZIKV. We found, instead, that the presence of AXL attenuated the ZIKV-induced activation of type I interferon (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes. Knocking out type I IFN receptor alpha chain (IFNAR1) restored the vulnerability of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor, in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL is unlikely to function as an entry receptor for ZIKV and may instead promote ZIKV infection in human astrocytes by antagonizing type I IFN signalling.
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| 3. |
- Chen, Jianqing
(författare)
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Radiolabeling and Biotinylation of Internalizing Monoclonal Antibody Chimeric BR96: Potential Use for Extracorporeal Immunoadsorption.
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, methodology of radiolabeling and simultaneous biotinylation for internalizing monoclonal antibody (MAb) chimeric BR96 (chiBR96) have been investigated by using three element groups of potential therapeutic radionuclides iodine, indium and rhenium, and their different labeling methods. The biodistribution and kinetics of biotinylated and radiolabeled chiBR96 have been studied in colon carcinoma isografted rats. The potential use of ECIA, based on the biotin-avidin concept, has been evaluated and compared with the approach of avidin "chase" in the same animal tumor model with respect to an enhancement of tumor-to-normal tissue (T/N) activity ratio. In vivo stability and tumor targeting capacity of biotinylated 111In-chiBR96 using the chelate SCN-Bz-CHX-A-DTPA, have increased compared with two other chelates used in this study. Conjugate NSTBB has been successfully used for iodination of chiBR96 combined with biotinylation, in contrast to the combination with electrophilic labeling method
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| 4. |
- Garkavij, Martin, et al.
(författare)
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Extracorporeal whole-blood immunoadsorption enhances radioimmunotargeting of iodine-125-labeled BR96-biotin monoclonal antibody
- 1997
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Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 38:6, s. 895-901
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the efficacy of tumor radioimmunotargeting with 125I-labeled BR96-biotin monoclonal antibody using a new method, whole-blood immunoadsorption (WBIA), based on direct adsorption of unbound monoclonal antibody (MAb) from blood without preceding separation of plasma. METHODS: Highly tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor-associated Lewis-type (Le(Y)) cell surface antigen. Forty-six Brown Norwegian male rats were inoculated intramuscularly and beneath the liver or kidney capsule with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, and investigated. The rats were injected intravenously with 3.5-4.5 MBq 125I-labeled BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 12 hr after injection. About six blood volumes were passed through an avidin-gel adsorption column during 2 hr. RESULTS: By using WBIA, whole-body radioactivity was reduced by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33 hr later, the activity uptake in tumors manifested only a nonsignificant decrease as compared with corresponding controls (p > 0.05) and had approximately similar time-activity curves. Uptake ratios for tumor (T):bone marrow, T:liver, T:kidney and T:lung were enhanced 2.3- to 3.5-fold in all three tumor models, as compared with controls. The ratio of liver tumor to bone marrow was improved from 10:1 to 30:1. CONCLUSION: This new method of WBIA yields significantly improved radioimmunotargeting of highly tumor-reactive, internalizing MAb BR96.
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