scholarly journals Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 837 ◽  
Author(s):  
Frakolaki ◽  
Kalliampakou ◽  
Kaimou ◽  
Moraiti ◽  
Kolaitis ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Infections ◽  
Physiological Role ◽  
Inverse Correlation ◽  
Dopa Decarboxylase ◽  
Hcv Rna ◽  
Virus Infections ◽  
Peripheral Tissues ◽  
Functional Complex

l-dopa decarboxylase (DDC) that catalyzes the biosynthesis of bioactive amines, such as dopamine and serotonin, is expressed in the nervous system and peripheral tissues, including the liver, where its physiological role remains unknown. Recently, we reported a physical and functional interaction of DDC with the major signaling regulator phosphoinosite-3-kinase (PI3K). Here, we provide compelling evidence for the involvement of DDC in viral infections. Studying dengue (DENV) and hepatitis C (HCV) virus infection in hepatocytes and HCV replication in liver samples of infected patients, we observed a negative association between DDC and viral replication. Specifically, replication of both viruses reduced the levels of DDC mRNA and the ~120 kDa SDS-resistant DDC immunoreactive functional complex, concomitant with a PI3K-dependent accumulation of the ~50 kDa DDC monomer. Moreover, viral infection inhibited PI3K-DDC association, while DDC did not colocalize with viral replication sites. DDC overexpression suppressed DENV and HCV RNA replication, while DDC enzymatic inhibition enhanced viral replication and infectivity and affected DENV-induced cell death. Consistently, we observed an inverse correlation between DDC mRNA and HCV RNA levels in liver biopsies from chronically infected patients. These data reveal a novel relationship between DDC and Flaviviridae replication cycle and the role of PI3K in this process.

scholarly journals Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

2021 ◽  
Vol 13 (3) ◽  
pp. 363-382
Author(s):  
Mario Dioguardi ◽  
Angela Pia Cazzolla ◽  
Claudia Arena ◽  
Diego Sovereto ◽  
Giorgia Apollonia Caloro ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Viral Disease ◽  
Receptor Expression ◽  
Virus Infections ◽  
Search Terms ◽  
Bibliographic Search ◽  
Meta Analyses

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

scholarly journals Az ösztrogénmetabolom biológiai és klinikai jelentősége lokális folyamatokban

2017 ◽  
Vol 158 (24) ◽  
pp. 929-937
Author(s):  
Krisztián Kovács ◽  
Barna Vásárhelyi ◽  
Katalin Mészáros ◽  
Attila Patócs ◽  
Gellért Karvaly
Keyword(s):  
Biological Activity ◽  
Clinical Significance ◽  
Physiological Role ◽  
Tissue Homeostasis ◽  
Diagnostic Significance ◽  
Peripheral Tissues ◽  
Breakdown Process ◽  
Specific Manner ◽  
Related Compounds

Abstract: Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929–937.

The role of PCSK9 in infectious diseases.

2021 ◽  
Vol 28 ◽  
Author(s):  
Laura Magnasco ◽  
Chiara Sepulcri ◽  
Roberta Maria Antonello ◽  
Stefano Di Bella ◽  
Laura Labate ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Malaria Infection ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Physiological Role ◽  
Protective Role ◽  
Loss Of Function ◽  
Pcsk9 Inhibition ◽  
Sepsis And Septic Shock

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, particularly regarding its role in lipid metabolism, cardiovascular risk, and its role in innate immunity. Increasing evidence is available about the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, and the regulation of host response to bacterial infections, primarily sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. Objective: This paper aims to review the available published literature on the role of PCSK9 in a wide array of infectious diseases. Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients to treat HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Finally, a loss of function in the PCSK9-encoding gene has been reported to reduce malaria infection mortality.

scholarly journals Transcriptional role of p53 in interferon-mediated antiviral immunity

2008 ◽  
Vol 205 (8) ◽  
pp. 1929-1938 ◽  
Author(s):  
César Muñoz-Fontela ◽  
Salvador Macip ◽  
Luis Martínez-Sobrido ◽  
Lauren Brown ◽  
Joseph Ashour ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Viral Replication ◽  
Viral Infections ◽  
Suppressor Gene ◽  
Central Component ◽  
Type I ◽  
Infected Cells

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.

scholarly journals Sex-Dependent Intestinal Replication of an Enteric Virus

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Christopher M. Robinson ◽  
Yao Wang ◽  
Julie K. Pfeiffer
Keyword(s):  
Gastrointestinal Tract ◽  
Viral Replication ◽  
Sex Hormones ◽  
Viral Infections ◽  
Type I Interferon ◽  
Enteric Virus ◽  
Interferon Response ◽  
Sex Bias ◽  
Type I ◽  
Peripheral Tissues

ABSTRACT Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine. In light of recent studies identifying intestinal factors, such as the microbiota, that alter enteric viral replication, we sought to investigate coxsackievirus replication within the intestine. Here, we orally infected mice with coxsackievirus B3 (CVB3) and found that CVB3 replication in the intestine is sex dependent. CVB3 replicated efficiently in the intestine of male mice but not female mice. Additionally, we found that the type I interferon response and sex hormones can alter both viral replication and lethality. Overall, these data suggest that sex and the immune response play a vital role in CVB3 replication in the intestine and should be considered in light of the sex bias observed in human disease. IMPORTANCE Sex bias in severe sequelae from enteric viral infections has been observed. Since viruses have evolved to achieve optimal levels of fitness in their environmental niches, it is imperative to study viruses at the site of initial replication. Here, we used an oral inoculation system for CVB3, which follows the natural route of infection in the gastrointestinal tract. We found that sex can influence the replication of CVB3 in the intestine. Additionally, the type I interferon response and sex hormones alter both CVB3 intestinal replication and lethality. Overall this work highlights the fact that sex should be considered in investigations of enteric viral replication and pathogenesis.

scholarly journals Probing the viral replication of HCV and XMRV : biochemical characterization, inhibition kinetics and role of host proteins in viral replication

2015 ◽  
Author(s):  
◽  
Tanyaradzwa P. Ndongwe
Keyword(s):  
Hepatitis C ◽  
Viral Replication ◽  
Reverse Transcriptase ◽  
Rna Binding ◽  
Biochemical Characterization ◽  
Hcv Rna ◽  
Hepatitis C Infection ◽  
Human Hepatoma Cells ◽  
Murine Leukemia

The studies described in this thesis focus on RNA viruses XMRV and HCV. In Chapter II we focused on Xenotropic Murine leukemia-Related Virus (XMRV). We characterized the biochemical activity and kinetics of the XMRV reverse transcriptase and discovered key mechanistic differences between XMRV, Moloney murine leukemia virus (MoMLV), and human immunodeficiency virus (HIV-1) reverse transcriptase (RT) enzymes. In Chapter III and IV we focused on Hepatitis C Virus (HCV), the causative agent of hepatitis C infection. We studied the role of an antiviral host factor Mov10 in the viral replication of HCV. We demonstrate that Mov10 overexpression in human hepatoma cells restricts HCV RNA production in a fully infectious virus cell culture system, leading to decreased virus production over time. Additionally, overexpression of Mov10 in producer cells decreases the infectivity of the produced virus. Confocal microscopy shows HCV infection results in redistribution of endogenous Mov10 to circular structures surrounding lipid droplets, proximal to viral proteins core and NS5A. Finally, we demonstrate that the RNA-binding function of Mov10 is responsible for its antiviral effect. Decreasing Mov10 protein expression levels decreased HCV replication and infection levels. Our data reveal a complex balance between Mov10 and HCV. In Chapter IV we studied several aspects of HCV. (i) We discovered two novel small molecule inhibitors of the HCV helicase that have antiviral function. (ii) We discovered that Dcp2 is a novel HCV host restriction factor that can block HCV replication, and (iii) we provide insights into the mechanism(s) of action of approved and clinically advanced direct-acting antiviral agents (DAAs).

Endogenous NUCB2/Nesfatin-1 Regulates Energy Homeostasis Under Physiological Conditions in Male Rats

2020 ◽  
Vol 52 (09) ◽  
pp. 676-684
Author(s):  
Anna-Maria Wilz ◽  
Kerstin Wernecke ◽  
Lena Appel ◽  
Johanna Kahrs ◽  
Riccardo Dore ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Calcium Binding ◽  
Energy Homeostasis ◽  
Physiological Role ◽  
Male Rats ◽  
Peripheral Tissues ◽  
Downstream Target ◽  
Food And Water Intake ◽  
Pharmacological Blockade

AbstractNesfatin-1 is the proteolytic cleavage product of Nucleobindin 2, which is expressed both in a number of brain nuclei (e. g., the paraventricular nucleus of the hypothalamus) and peripheral tissues. While Nucleobindin 2 acts as a calcium binding protein, nesfatin-1 was shown to affect energy homeostasis upon central nervous administration by decreasing food intake and increasing thermogenesis. In turn, Nucleobindin 2 mRNA expression is downregulated in starvation and upregulated in the satiated state. Still, knowledge about the physiological role of endogenous Nucleobindin 2/nesfatin-1 in the control of energy homeostasis is limited and since its receptor has not yet been identified, rendering pharmacological blockade impossible. To overcome this obstacle, we tested and successfully established an antibody-based experimental model to antagonize the action of nesfatin-1. This model was then employed to investigate the physiological role of endogenous Nucleobindin 2/nesfatin-1. To this end, we applied nesfatin-1 antibody into the paraventricular nucleus of satiated rats to antagonize the presumably high endogenous Nucleobindin 2/nesfatin-1 levels in this feeding condition. In these animals, nesfatin-1 antibody administration led to a significant decrease in thermogenesis, demonstrating the important role of endogenous Nucleobindin 2/nesfatin-1in the regulation of energy expenditure. Additionally, food and water intake were significantly increased, confirming and complementing previous findings. Moreover, neuropeptide Y was identified as a major downstream target of endogenous Nucleobindin 2/nesfatin-1.

scholarly journals The Inhibitory Role of B7-H4 in Antitumor Immunity: Association with Cancer Progression and Survival

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Changjun He ◽  
Haiquan Qiao ◽  
Hongchi Jiang ◽  
Xueying Sun
Keyword(s):  
Cancer Progression ◽  
Antitumor Immunity ◽  
Human Cancer ◽  
Physiological Role ◽  
T Cell Response ◽  
Soluble Form ◽  
Peripheral Tissues ◽  
Inhibitory Role ◽  
Pertinent Data

B7-H4 is one of the most recently identified members of B7 superfamily of costimulatory molecules serving as an inhibitory modulator of T-cell response. B7-H4 is broadly expressed in human peripheral tissues and inducibly expressed in immune cells. The expression of B7-H4 has been observed in various types of human cancer tissues, and its soluble form has been detected in blood samples from cancer patients. However, its precise physiological role is still elusive, as its receptor has not been identified and the expression levels are not consistent. This paper summarizes the pertinent data on the inhibitory role of B7-H4 in antitumor immunity and its association with cancer progression and survival in human patients. The paper also discusses the clinical significance of investigating B7-H4 as potential markers for cancer diagnosis and prognosis, and as therapeutic targets.

scholarly journals Gamma Delta T Cells and Their Involvement in COVID-19 Virus Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Georg von Massow ◽  
Steve Oh ◽  
Alan Lam ◽  
Kenth Gustafsson
Keyword(s):  
T Cells ◽  
Viral Infections ◽  
Cell Subset ◽  
Γδ T Cells ◽  
Common Symptom ◽  
Virus Infections ◽  
Infected Cells ◽  
The Relationship

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical αβ T cells. However, another subset of T cells called γδ T cells could have an important role to play. As part of the innate immune system, γδ T cells respond to inflammation and stressed or infected cells. The γδ T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because γδ T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for γδ T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cells in vitro. γδ T cells can take up, process and present antigens from microbes and human cells. As e.g. tumour-associated antigens are presented by MHC on γδ T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. γδ T cells are already used for medical purposes in oncology and have potential in cancer therapy. As γδ T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and γδ T cells.

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