14 results
Search Results
2. Brain HIV-1 latently-infected reservoirs targeted by the suicide gene strategy.
- Author
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Saeb, Sepideh, Ravanshad, Mehrdad, Pourkarim, Mahmoud Reza, Daouad, Fadoua, Baesi, Kazem, Rohr, Olivier, Wallet, Clémentine, and Schwartz, Christian
- Subjects
HIV ,GENE targeting ,CENTRAL nervous system ,GENOME editing ,T cells - Abstract
Reducing the pool of HIV-1 reservoirs in patients is a must to achieve functional cure. The most prominent HIV-1 cell reservoirs are resting CD4 + T cells and brain derived microglial cells. Infected microglial cells are believed to be the source of peripheral tissues reseedings and the emergence of drug resistance. Clearing infected cells from the brain is therefore crucial. However, many characteristics of microglial cells and the central nervous system make extremely difficult their eradication from brain reservoirs. Current methods, such as the "shock and kill", the "block and lock" and gene editing strategies cannot override these difficulties. Therefore, new strategies have to be designed when considering the elimination of brain reservoirs. We set up an original gene suicide strategy using latently infected microglial cells as model cells. In this paper we provide proof of concept of this strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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3. Correction to: Pulmonary edema following central nervous system lesions induced by a non-mouse-adapted EV71 strain in neonatal BALB/c mice.
- Author
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Jin, Yuefei, Zhang, Chao, Zhang, Rongguang, Ren, Jingchao, Chen, Shuaiyin, Sui, Meili, Zhou, Guangyuan, Dang, Dejian, Zhu, Jiehui, Feng, Huifen, Xi, Yuanlin, Yang, Haiyan, and Duan, Guangcai
- Subjects
CENTRAL nervous system ,PULMONARY edema ,MICE - Abstract
An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation
- Author
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Ridha, Mohamed, Jones, Dylan G., Lerner, David P., Vytopil, Michal, Voetsch, Barbara, Burns, Joseph D., Ramineni, Anil, and Raibagkar, Pooja
- Published
- 2021
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5. Microglia play an important role in PRV infection-induced immune responses of the central nervous system
- Author
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Sun, Xiuxiu, Jin, Xinxin, Liu, Xi, Wang, Lumeng, Li, Li, Yang, Junjie, Feng, Helong, Lin, Zhengdan, Zhan, Cunlin, Zhang, Wanpo, Gu, Changqin, Hu, Xueying, Liu, Xiaoli, and Cheng, Guofu
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- 2023
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6. Genetic characterization of atypical porcine pestivirus from neonatal piglets with congenital tremor in Hubei province, China.
- Author
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Ren, Xujiao, Qian, Ping, Hu, Zihui, Chen, Huanchun, and Li, Xiangmin
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PIGLETS ,CHLOROPLAST DNA ,TREMOR ,CENTRAL nervous system ,GENETIC variation ,SWINE farms ,SEQUENCE analysis - Abstract
Background: Atypical porcine pestivirus (APPV) is a single-stranded RNA virus with high genetic variation that causes congenital tremor (CT) in newborn piglets, belonging to the genus Pestivirus of the family Flaviviridae. Increasing cases of APPV infection in China in the past few years would pose severe challenges to the development of pig production. In view of the high genetic variability of APPV, the genetic characteristics of APPV in Hubei province was determined. Methods: 52 tissue samples from 8 CT-affected newborn piglets were collected at two different periods in the same pig farm in Hubei province. Viral nucleic acid was extracted to detect pathogens that can cause CT in piglets or other common clinical pathogens by RT-PCR. Haematoxylin and eosin (HE) staining, immunohistochemical (IHC) analysis, and qRT-PCR were performed to observe histopathological changes and histological distribution, and detect the viral load of APPV in CT-affected piglets. The full-length genome of APPV was obtained and sequence analysis was conducted to determine the phylogenetic relationship. Results: Histopathological observation and histological distribution analysis showed that the histological lesions and distribution of APPV were mainly in central nervous system (CNS) tissues and immune tissues. Viral load analysis revealed that the viral copy number was higher in the cerebellum, submaxillary lymph nodes, tonsil, and serum than in other tissues. Phylogenetic analysis showed that CH-HB2020 and CH-HB2021 belonged to Clade I.3, and is most closely related to APPV_CH-GX2016. Sequence alignment based on APPV encoding sequences (CDS) showed that the nucleotide identities of CH-HB2020 or CH-HB2021 with Clade I, Clade II, and Clade III strains were 83.5–98.6%, 83.1–83.5%, and 81.1–81.4%, respectively, while the amino acid identities were 91.9–99.2%, 91.2–95.3%, and 90.77–91.4%, respectively. No recombination event was observed in CH-HB2020 or CH-HB2021 strains. Conclusions: These findings enhance our understanding of the pathogenesis of APPV and may provide potential molecular evidence for its prevalence and transmission. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Anti-HSV-1 activity of Aspergillipeptide D, a cyclic pentapepetide isolated from fungus Aspergillus sp. SCSIO 41501.
- Author
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Wang, Zhaoyang, Jia, Jiaoyan, Wang, Lu, Li, Feng, Wang, Yiliang, Jiang, Yuzhou, Song, Xiaowei, Qin, Shurong, Zheng, Kai, Ye, Ju, Ren, Zhe, Wang, Yifei, and Qi, Shuhua
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GOLGI apparatus ,HERPES simplex virus ,VIRAL proteins ,DNA replication ,ASPERGILLUS ,RNA synthesis ,CENTRAL nervous system - Abstract
Background: Herpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501, At present, there are many studies on the anti-tumor, anti-clotting, anti-oxidant and immunoinflammatory effects of Aspergillipeptide D, but little research has been done on the anti-HSV-1 activity of Aspergillipeptide D. Methods: The anti-HSV-1 activity of Aspergillipeptide D was evaluated by plaque reduction assay. The mechanism of action against HSV-1 was determined from the effective stage. Then we assayed the viral DNA replication, viral RNA synthesis and protein expression, respectively. We also identified the proteins that interact with gB by mass spectrometry, and assayed the effect of Aspergillipeptide D on the interaction between the virus gB protein and cell proteins. Results: Plaque reduction experiments showed that Aspergillipeptide D did not affect HSV-1 early infection events, including viral inactivation, attachment and penetration. Interestingly, Aspergillipeptide D dramatically reduced both the gene and protein levels of viral late protein gB, and suppressed its location in the endoplasmic reticulum and Golgi apparatus. In contrast, overexpression of gB restored viral production. Finally, proteomic analysis revealed that the numbers of cellular proteins that interacted with gB protein was largely decreased by Aspergillipeptide D. These results suggested that Aspergillipeptide D inhibited gB function to affect HSV-1 intercellular spread. Conclusions: Our results indicated that Aspergillipeptide D might be a potential candidate for HSV-1 therapy, especially for ACV-resistant strains. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Pulmonary edema following central nervous system lesions induced by a non- mouse-adapted EV71 strain in neonatal BALB/c mice
- Author
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Jin, Yuefei, Zhang, Chao, Zhang, Rongguang, Ren, Jingchao, Chen, Shuaiyin, Sui, Meili, Zhou, Guangyuan, Dang, Dejian, Zhu, Jiehui, Feng, Huifen, Xi, Yuanlin, Yang, Haiyan, and Duan, Guangcai
- Published
- 2017
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9. Correction to: Pulmonary edema following central nervous system lesions induced by a non-mouse-adapted EV71 strain in neonatal BALB/c mice
- Author
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Huifen Feng, Chao Zhang, Rongguang Zhang, Haiyan Yang, Jiehui Zhu, Jing-chao Ren, Meili Sui, Guangcai Duan, Yuanlin Xi, Guangyuan Zhou, Shuaiyin Chen, Yuefei Jin, and Dejian Dang
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Pathology ,medicine.medical_specialty ,biology ,Strain (biology) ,Central nervous system ,Pulmonary edema ,medicine.disease ,biology.organism_classification ,Virology ,BALB/c ,lcsh:Infectious and parasitic diseases ,Infectious Diseases ,medicine.anatomical_structure ,medicine ,lcsh:RC109-216 - Abstract
An amendment to this paper has been published and can be accessed via the original article.
- Published
- 2021
10. Brain HIV-1 latently-infected reservoirs targeted by the suicide gene strategy
- Author
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Fadoua Daouad, Christian Schwartz, Sepideh Saeb, Mehrdad Ravanshad, Clémentine Wallet, Kazem Baesi, Mahmoud Reza Pourkarim, and Olivier Rohr
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,Central nervous system ,Cell ,Human immunodeficiency virus (HIV) ,Short Report ,HIV Infections ,Drug resistance ,Infectious and parasitic diseases ,RC109-216 ,Biology ,medicine.disease_cause ,ASTROCYTES ,ACTIVATION ,MICROGLIA ,03 medical and health sciences ,0302 clinical medicine ,Latent reservoirs ,Genome editing ,Virology ,medicine ,Humans ,MACROPHAGES ,Gene ,Cells, Cultured ,REACTIVATION ,Gene Editing ,Science & Technology ,Microglia ,Genes, Transgenic, Suicide ,Brain ,Suicide gene ,BARRIER ,Virus Latency ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Microglial ,CTIP2 ,Immunology ,REPLICATION ,HIV-1 ,Life Sciences & Biomedicine ,030217 neurology & neurosurgery - Abstract
Several strategies are currently investigated to reduce the pool of all HIV-1 reservoirs in infected patients in order to achieve functional cure. The most prominent HIV-1 cell reservoirs in the brain are microglial cells. Virus infection maybe lifelong. Infected microglial cells are believed to be the source of peripheral tissues reseeding and responsible for the emergence of drug resistance. Clearing infected cells from the brain is therefore crucial. However, many characteristics of microglial cells and the central nervous system prevent the eradication of brain reservoirs. Current trials, such as “shock and kill”, the “deep and lock” and the gene editing strategies do not respond to these difficulties. Therefore, new strategies have to be designed when considering brain reservoirs such as microglial cells. We set up an original gene suicide strategy using a latently infected microglial model. In this paper we provide proof of concept of this strategy. Our results demonstrate that this strategy enables the eradication of latently-infected microglial cells.
- Published
- 2020
11. Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification.
- Author
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Lauterbach, Henning, Truong, Phi, and McGavern, Dorian B.
- Subjects
VIRUS diseases ,COMMUNICABLE diseases ,CENTRAL nervous system ,LYMPHOCYTIC choriomeningitis virus ,ARENAVIRUSES ,IMMUNE response - Abstract
Once a virus infection establishes persistence in the central nervous system (CNS), it is especially difficult to eliminate from this specialized compartment. Therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the CNS by the adaptive immune system. Such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (LCMV) referred to as clone 13. In this study we demonstrate that following intravenous inoculation, clone 13 rapidly infected peripheral tissues within one week, but more slowly inundated the entire brain parenchyma over the course of a month. During the establishment of persistence, we observed that genetically tagged LCMV-specific cytotoxic T lymphocytes (CTL) progressively lost function; however, the severity of this loss in the CNS was never as substantial as that observed in the periphery. One of the most impressive features of this model system is that the peripheral T cell response eventually regains functionality at ∼60-80 days post-infection, and this was associated with a rapid decline in virus from the periphery. Coincident with this "reanimation phase" was a massive influx of CD4 T and B cells into the CNS and a dramatic reduction in viral distribution. In fact, olfactory bulb neurons served as the last refuge for the persisting virus, which was ultimately purged from the CNS within 200 days post-infection. These data indicate that a functionally revived immune response can prevail over a virus that establishes widespread presence both in the periphery and brain parenchyma, and that therapeutic enhancement of an existing response could serve as an effective means to thwart long term CNS persistence. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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12. Transplacental murine cytomegalovirus infection in the brain of SCID mice.
- Author
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Woolf, Nigel K., Jaquish, Dawn V., and Koehrn, Fred J.
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CYTOMEGALOVIRUS diseases ,HERPESVIRUS diseases ,VIRUS diseases ,CENTRAL nervous system ,LABORATORY mice ,CELLULAR immunity - Abstract
Background: Congenital cytomegalovirus (CMV) infection is the most common congenital viral infection in humans and the major nonhereditary cause of central nervous system (CNS) developmental disorders. Previous attempts to develop a murine CMV (MCMV) model of natural congenital human CMV (HCMV) infection have failed because MCMV does not cross the placenta in immunocompetent mice. Results: In marked contrast with immunocompetent mice, C.B-17 SCID (severe combined immunodeficient) mice were found to be highly susceptible to natural MCMV transplacental transmission and congenital infection. Timed-pregnant SCID mice were intraperitoneally (IP) injected with MCMV at embryonic (E) stages E0-E7, and vertical MCMV transmission was evaluated using nested polymerase chain reaction (nPCR), in situ hybridization (ISH) and immunohistochemical (IHC) assays. SCID mouse dams IP injected at E0 with 10
2 PFU of MCMV died or resorbed their fetuses by E18. Viable fetuses collected at E18 from SCID mice IP injected with 102 -104 PFU of MCMV at E7 did not demonstrate vertical MCMV transmission. Notably, transplacental MCMV transmission was confirmed in E18 fetuses from SCID mice IP injected with 103 PFU of MCMV at stages E3-E5. The maximum rate of transplacental MCMV transmission (53%) at E18 occurred when SCID mouse dams were IP injected with 103 PFU of MCMV at E4. Congenital infection was confirmed by IHC immunostaining of MCMV antigens in 26% of the MCMV nPCR positive E18 fetuses. Transplacental MCMV transmission was associated with intrauterine growth retardation and microcephaly. Additionally, E18 fetuses with MCMV nPCR positive brains had cerebral interleukin-1α (IL-1α) expression significantly upregulated and cerebral IL-1 receptor II (IL-1RII) transcription significantly downregulated. However, MCMV-induced changes in cerebral cytokine expression were not associated with any histological signs of MCMV infection or inflammation in the brain. Conclusion: Severe T- and B-cell immunodeficiencies in SCID mice significantly enhance the rate of natural MCMV transplacental transmission and congenital infection. During gestation MCMV exhibits a tissue tropism for the developing brain, and vertical MCMV transmission is correlated with fetal growth retardation and abnormal cerebral proinflammatory cytokine expression. These data confirm that natural vertical MCMV infection in SCID mice constitutes a useful new experimental rodent model of congenital HCMV infection. [ABSTRACT FROM AUTHOR]- Published
- 2007
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13. Shell Vial culture Assay for the rapid diagnosis of Japanese encephalitis, West Nile and Dengue-2 viral encephalitis.
- Author
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Jayakeerthi, Rangaiah S., Potula, Raghava V., Srinivasan, S., and Badrinath, S.
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JAPANESE B encephalitis ,CENTRAL nervous system ,IMMUNOGLOBULINS ,IMMUNOFLUORESCENCE ,ANTIGENS ,ETIOLOGY of diseases - Abstract
Background: Encephalitis caused by flaviviruses, Japanese encephalitis virus (JEV) and West Nile virus (WNV) is responsible for significant morbidity and mortality in many endemic countries. Dengue-2 (Den-2) virus is a recent addition to the list of encephalitogenic viruses, after its Central Nervous System (CNS) invasion capability has been established. There is a wide array of laboratory tools that have helped us not only in the diagnosis of these conditions but also in understanding their pathogenesis and pathology. However, there are no reports of Shell Vial Culture (SVC), a centrifuge enhanced tissue culture assay that has revolutionized viral culturing in terms of rapidity and sensitivity being optimized for these flaviviral encephalitic conditions. The present study is an attempt to standardize and evaluate the usefulness of SVC for the laboratory diagnosis of JE, WN and Den-2 encephalitis cases and to compare it with Indirect Immunofluorescence (IIF) technique that detects cell associated virus antigen. Analysis of the various clinical parameters with respect to viral etiology has also been carried out. Results: Pediatric patients constituted the major group involved in the study (92%). Etiological diagnosis of viral encephalitis could be established in twenty nine (58%) patients. JE encephalitis was the commonest with 19 (39%) cases being positive followed by, WN (9 cases-18%) and Den-2 (one case). IIF test could detect antigens of JE, WN and Den-2 viruses in 16(32%), 7(14%) and 1 case respectively. Shell vial culture assay picked up all cases that were positive by IIF test. In addition, SVC assay could detect 3 and 2 more cases of JE and WN encephalitis respectively, that were negative by the IIF test. Conclusion: Shell vial culture is a rapid and efficient tool for the etiological diagnosis of JE, WN and Den-2 encephalitis cases. Early, prompt collection, transport and processing of the CSF samples, would make SVC a better method for the rapid diagnosis of these flaviviral infections. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
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14. A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted complement inhibitor
- Author
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Stephen Tomlinson, Carl Atkinson, Chuanfu Zhang, Chaojie Yang, Liuyu Huang, Nan Liu, Lixue Song, Jian Wang, Su Wenli, Zhongqiang Wang, Fei Qiao, Zhenjun Li, Hongbin Song, Guang Yang, Yansong Sun, Yong Wang, Leili Jia, Jing Li, and Shaofu Qiu
- Subjects
medicine.medical_treatment ,Recombinant Fusion Proteins ,Central nervous system ,Inflammation ,Biology ,lcsh:Infectious and parasitic diseases ,Complement inhibitor ,Mice ,Virology ,medicine ,Animals ,lcsh:RC109-216 ,Receptor ,Spinal cord injury ,Neurogenic inflammation ,Biological Products ,Mice, Inbred ICR ,Hypothesis ,medicine.disease ,Complement system ,Enterovirus A, Human ,Receptors, Complement ,Disease Models, Animal ,medicine.anatomical_structure ,Cytokine ,Treatment Outcome ,Infectious Diseases ,Immunology ,Receptors, Complement 3b ,Receptors, Complement 3d ,medicine.symptom ,Neurogenic Inflammation ,Immunosuppressive Agents - Abstract
Background Enterovirus 71 (EV71), one of the most important neurotropic EVs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The neurological diseases are attributed to infection by EV71 inducing an extensive peripheral and central nervous system (CNS) inflammatory response with abnormal cytokine production and lymphocyte depletion induced by EV71 infection. In the absence of specific antiviral agents or vaccines, an effective immunosuppressive strategy would be valuable to alleviate the severity of the local inflammation induced by EV71 infection. Presentation of the hypothesis The complement system plays a pivotal role in the inflammatory response. Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. CR2-targeted complement inhibition has been proved to be a potential therapeutic strategy for many diseases, such as influenza virus-induced lung tissue injury, postischemic cerebral injury and spinal cord injury. In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry) is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation. Testing the hypothesis CR2-Crry is expressed in CHO cells, and its biological activity is determined by complement inhibition assays. 7-day-old ICR mice are inoculated intracranially with EV71 to duplicate the neurological symptoms. The mice are then divided into two groups, in one of which the mice are treated with CR2-Crry targeted complement inhibitor, and in the other with phosphate-buffered saline. A group of mice deficient in complement C3, the breakdown products of which bind to CR2, are also infected with EV71 virus. The potential bioavailability and efficacy of the targeted complement inhibitor are evaluated by histology, immunofluorescence staining and radiolabeling. Implications of the hypothesis CR2-Crry-mediated targeting complement inhibition will alleviate the local inflammation and provide an effective treatment for the severe neurological diseases associated with EV71 infection.
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