The Experts below are selected from a list of 22944 Experts worldwide ranked by ideXlab platform
Guangxiang Luo - One of the best experts on this subject based on the ideXlab platform.
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characterization of Apolipoprotein C1 in hepatitis c virus infection and morphogenesis
Virology, 2018Co-Authors: Han Zhang, Luhua Qiao, Guangxiang LuoAbstract:Abstract Previous studies have shown that Apolipoprotein C1 (apoC1)-specific antibodies precipitated hepatitis C virus (HCV) and neutralized HCV infectivity, suggesting that apoC1 is a HCV component. However, the importance of apoC1 in the HCV life cycle has not been experimentally examined. In the present study, we sought to determine the role of apoC1 in the HCV infection and morphogenesis by knocking out the apoC1 gene using the CRISPR/Cas9 system. Strikingly, apoC1 gene knockout markedly enhanced apoE expression. As a result, apoC1 gene knockout per se didn’t significantly affect HCV infection or morphogenesis, probably ascribing to its redundant functions with apoE. However, knockout of apoC1 gene potentiated the impairment of HCV infection and/or morphogenesis by apoE-specific small interfering RNAs. Additionally, a recombinant apoC1 protein efficiently blocked HCV infection. Collectively, these findings suggest that apoC1 and apoE have redundant functions in the HCV infection and morphogenesis.
Jeanchristophe Meunier - One of the best experts on this subject based on the ideXlab platform.
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Apolipoprotein C1 association with hepatitis c virus
Journal of Virology, 2008Co-Authors: Jeanchristophe Meunier, Kristina Faulk, Ronald E Engle, Robert H Purcell, Rodney S Russell, Suzanne U EmersonAbstract:Accumulating evidence suggests that cellular lipoprotein components are involved in hepatitis C virus (HCV) morphogenesis, but the precise contribution of these components remains unclear. We investigated the involvement of Apolipoprotein C1 (ApoC1) in HCV infection in the HCV pseudotyped particle system (HCVpp), in the recently developed cell culture infection model (HCVcc), and in authentic HCV isolated from viremic chimpanzees. Viral genomes associated with HCVcc or authentic HCV were efficiently immunoprecipitated by anti-ApoC1, demonstrating that ApoC1 was a normal component of HCV. The infectivities of HCVpp that had been mixed with ApoC1 and, more importantly, untreated HCVcc collected from lysates or media of infected Huh7.5 cells were directly neutralized by anti-ApoC1. Indeed, convalescent anti-HCV immunoglobulin G and anti-ApoC1 each neutralized over 75% of infectious HCVcc particles, indicating that many, if not all, infectious particles were recognized by both antibodies. Moreover, peptides corresponding to the C-terminal region of ApoC1 blocked infectivity of both HCVpp and HCVcc. Altogether, these results suggest that ApoC1 associates intracellularly via its C-terminal region with surface components of virions during viral morphogenesis and may play a major role in the replication cycle of HCV.
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evidence for cross genotype neutralization of hepatitis c virus pseudo particles and enhancement of infectivity by Apolipoprotein C1
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Jeanchristophe Meunier, Kristina Faulk, Ronald E Engle, Ming Zhao, Birke Bartosch, Harvey J Alter, Suzanne U Emerson, Francoisloic Cosset, Robert H Purcell, Jens BukhAbstract:The lack of a cell culture system to support hepatitis C virus (HCV) replication has hampered studies of this frequent cause of chronic liver disease. However, pseudotyped retroviral particles (pp) bearing the HCV envelope glycoproteins have provided a different approach to HCV studies. We used genotype 1a pp to detect neutralizing antibodies (NtAb) in eight chimpanzees and four humans infected with 1a strains, and developed pp of genotypes 2a, 3a, 4a, 5a, and 6a to study crossreactivity. NtAb was detected in one of four chimpanzees and none of three humans with acute resolving infection, suggesting that NtAb is not required for HCV clearance. NtAb were detected at high titer in two of four chimpanzees and, in Patient H, all with persistent infection; responses paralleled humoral responses to envelope 1 and 2 proteins and, in some cases, correlate also with antibodies to the hypervariable region 1, previously thought to be the primary site of neutralization. NtAb raised during 1a infections could neutralize HCVpp of genotypes 4a, 5a, and 6a but had only limited reactivity against 2a and 3a. The detection of high-titer NtAb with cross-genotype reactivity has important implications for the development of active and passive immune-prophylaxis strategies against HCV. Finally, we found that HCVpp infectivity was enhanced by human or chimpanzee sera; Apolipoprotein C1 alone or as a component of high-density lipoproteins caused this enhancement. Future studies of the in vivo role of Apolipoprotein C1 might provide additional insights into the infection process of HCV.
Lind Anne-li - One of the best experts on this subject based on the ideXlab platform.
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CSF levels of Apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia
'Dove Medical Press Ltd.', 2019Co-Authors: Lind Anne-li, Just David, Mikus Maria, Fredolini Claudia, Ioannou Marina, Gerdle Bjorn, Ghafouri Bijar, Backryd Emmanuel, Tanum Lars, Gordh TorstenAbstract:Objective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. Results: We found increased levels of Apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders
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CSF levels of Apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia
'Dove Medical Press Ltd.', 2019Co-Authors: Lind Anne-li, Just David, Mikus Maria, Fredolini Claudia, Ioannou Marina, Gerdle Bjorn, Ghafouri Bijar, Backryd Emmanuel, Tanum Lars, Gordh TorstenAbstract:Objective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. Results: We found increased levels of Apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders.Funding Agencies|Swedish Governmental Agency for Innovation SystemsVinnova; Swedish Research Council (Vetenskapsradet)Swedish Research Council; Uppsala University; KTH Center for Applied Precision Medicine (KCAP); Marie-Curie fellowship from the INSENS/FP7-PEOPLE-2013European Union (EU) [607616]; NEURO Sweden; AFA Insurance; ALF Grants, Region Ostergotland
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Biomarkers for Better Understanding of the Pathophysiology and Treatment of Chronic Pain : Investigations of Human Biofluids
'Uppsala University', 2017Co-Authors: Lind Anne-liAbstract:Chronic pain affects 20 % of the global population, causes suffering, is difficult to treat, and constitutes a large economic burden for society. So far, the characterization of molecular mechanisms of chronic pain-like behaviors in animal models has not translated into effective treatments. In this thesis, consisting of five studies, pain patient biofluids were analyzed with modern proteomic methods to identify biomarker candidates that can be used to improve our understanding of the pathophysiology chronic pain and lead to more effective treatments. Paper I is a proof of concept study, where a multiplex solid phase-proximity ligation assay (SP-PLA) was applied to cerebrospinal fluid (CSF) for the first time. CSF reference protein levels and four biomarker candidates for ALS were presented. The investigated proteins were not altered by spinal cord stimulation (SCS) treatment for neuropathic pain. In Paper II, patient CSF was explored by dimethyl and label-free mass spectrometric (MS) proteomic methods. Twelve proteins, known for their roles in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity, were identified to be associated with SCS treatment of neuropathic pain. In Paper III, proximity extension assay (PEA) was used to analyze levels of 92 proteins in serum from patients one year after painful disc herniation. Patients with residual pain had significantly higher serum levels of 41 inflammatory proteins. In Paper IV, levels of 55 proteins were analyzed by a 100-plex antibody suspension bead array (ASBA) in CSF samples from two neuropathic pain patient cohorts, one cohort of fibromyalgia patients and two control cohorts. CSF protein profiles consisting of levels of Apolipoprotein C1, ectonucleotide pyrophosphatase/phosphodiesterase family member 2, angiotensinogen, prostaglandin-H2 D-isomerase, neurexin-1, superoxide dismutases 1 and 3 were found to be associated with neuropathic pain and fibromyalgia. In Paper V, higher CSF levels of five chemokines and LAPTGF-beta-1were detected in two patient cohorts with neuropathic pain compared with healthy controls. In conclusion, we demonstrate that combining MS proteomic and multiplex antibody-based methods for analysis of patient biofluid samples is a viable approach for discovery of biomarker candidates for the pathophysiology and treatment of chronic pain. Several biomarker candidates possibly reflecting systemic inflammation, lipid metabolism, and neuroinflammation in different pain conditions were identified for further investigation.Uppsala Berzelii Technology Centre for Neurodiagnostic
Gordh Torsten - One of the best experts on this subject based on the ideXlab platform.
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CSF levels of Apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia
'Dove Medical Press Ltd.', 2019Co-Authors: Lind Anne-li, Just David, Mikus Maria, Fredolini Claudia, Ioannou Marina, Gerdle Bjorn, Ghafouri Bijar, Backryd Emmanuel, Tanum Lars, Gordh TorstenAbstract:Objective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. Results: We found increased levels of Apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders
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CSF levels of Apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia
'Dove Medical Press Ltd.', 2019Co-Authors: Lind Anne-li, Just David, Mikus Maria, Fredolini Claudia, Ioannou Marina, Gerdle Bjorn, Ghafouri Bijar, Backryd Emmanuel, Tanum Lars, Gordh TorstenAbstract:Objective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. Results: We found increased levels of Apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders.Funding Agencies|Swedish Governmental Agency for Innovation SystemsVinnova; Swedish Research Council (Vetenskapsradet)Swedish Research Council; Uppsala University; KTH Center for Applied Precision Medicine (KCAP); Marie-Curie fellowship from the INSENS/FP7-PEOPLE-2013European Union (EU) [607616]; NEURO Sweden; AFA Insurance; ALF Grants, Region Ostergotland
Jens Bukh - One of the best experts on this subject based on the ideXlab platform.
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evidence for cross genotype neutralization of hepatitis c virus pseudo particles and enhancement of infectivity by Apolipoprotein C1
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Jeanchristophe Meunier, Kristina Faulk, Ronald E Engle, Ming Zhao, Birke Bartosch, Harvey J Alter, Suzanne U Emerson, Francoisloic Cosset, Robert H Purcell, Jens BukhAbstract:The lack of a cell culture system to support hepatitis C virus (HCV) replication has hampered studies of this frequent cause of chronic liver disease. However, pseudotyped retroviral particles (pp) bearing the HCV envelope glycoproteins have provided a different approach to HCV studies. We used genotype 1a pp to detect neutralizing antibodies (NtAb) in eight chimpanzees and four humans infected with 1a strains, and developed pp of genotypes 2a, 3a, 4a, 5a, and 6a to study crossreactivity. NtAb was detected in one of four chimpanzees and none of three humans with acute resolving infection, suggesting that NtAb is not required for HCV clearance. NtAb were detected at high titer in two of four chimpanzees and, in Patient H, all with persistent infection; responses paralleled humoral responses to envelope 1 and 2 proteins and, in some cases, correlate also with antibodies to the hypervariable region 1, previously thought to be the primary site of neutralization. NtAb raised during 1a infections could neutralize HCVpp of genotypes 4a, 5a, and 6a but had only limited reactivity against 2a and 3a. The detection of high-titer NtAb with cross-genotype reactivity has important implications for the development of active and passive immune-prophylaxis strategies against HCV. Finally, we found that HCVpp infectivity was enhanced by human or chimpanzee sera; Apolipoprotein C1 alone or as a component of high-density lipoproteins caused this enhancement. Future studies of the in vivo role of Apolipoprotein C1 might provide additional insights into the infection process of HCV.