scholarly journals Hepatitis C Virus E1 Protein Enhances Macrophage iNOS Expression In Vitro

2021 ◽  
Author(s):  
Batkhishig Munkhjargal ◽  
Bilguun Enkhtuvshin ◽  
Uranbileg Ulziisaikhan ◽  
Baljinnyam Tuvdenjamts ◽  
Khulan Unurbuyan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Response ◽  
Inos Expression ◽  
No Production ◽  
E1 Protein ◽  
Ifn Γ

AbstractObjectiveHepatitis C virus (HCV) is a single-stranded RNA virus that causes chronic hepatitis, cirrhosis, and liver cancer. Approximately 170 million individuals are infected with HCV worldwide. The pathogenesis of HCV-associated liver injury is thought to be due to the host antiviral immune response, including the T cell response, and excessive production of proinflammatory cytokines, reactive oxygen species, and nitric oxide (NO).Interferon-γ (IFN-γ) is a key cytokine in the adaptive immune response that is primarily secreted from CD4+ T helper cells to induce cytotoxic T lymphocyte (CTL) cell response against HCV infection. Another important role of IFN-γ is the activation of macrophages in the liver resulting in inhibition of viral replication and increased NO production.Enhanced inducible nitric oxide synthase (iNOS) expression and NO production observed in the liver of HCV-infected patients is positively correlated with viral load and hepatic inflammation. HCV-infected macrophages are major producers of NO in the liver. It is not completely understood how HCV proteins affect iNOS expression and what the role of IFN-γ is in HCV protein expression in HCV-infected macrophages. In this study, we examined the effect of INF-γ and HCV proteins on iNOS expression in the Raw264.7 cell line.ResultsConsistent with other studies, HCV core and NS5A proteins induced iNOS expression in macrophages. Moreover, HCV E1 protein-enhanced iNOS expression is highest in the presence and absence of IFN-γ activation.ConclusionThese results indicate that hepatitis C virus core, NS5A, E1 protein regulates iNOS protein expression in IFN-γ-activated and resting macrophage cell lines. These findings points to a future research direction for understanding the pathogenesis of HCV-related liver inflammation.

scholarly journals Formal modeling of the key determinants of Hepatitis C Virus (HCV) induced adaptive immune response network: An integrative approach to map the cellular and cytokine-mediated host immune regulations

2018 ◽  
Author(s):  
Ayesha Obaid ◽  
Anam Naz ◽  
Shifa Tariq Ashraf ◽  
Faryal Mehwish Awan ◽  
Aqsa Ikram ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Biological Data ◽  
Signaling Networks ◽  
Host Immune System ◽  
Adaptive Immune ◽  
Ifn Γ

Background. Hepatitis C Virus (HCV) is a major causative agent of liver infection leading to critical liver damage. In response to HCV, the improper regulation of host immune system leads to chronic infection. The host immune system employs multiple cell types, diverse variety of cytokine mediators and interacting signaling networks to neutralize the HCV infection. To understand the complexity of the interactions within the immune signaling networks, systems biology provides an efficient alternative approach. Integrating such approaches with immunology and virology helps to study highly complex immune regulatory networks within the host and presents a concise view of the whole system. Methods. Initially, a logic-based diagram is generated based on multiple reported interactions between immune cells and cytokines during host immune response to HCV. Furthermore, an abstracted sub-network is modeled qualitatively which consists of both the key cellular and cytokine components of the HCV induced immune system. Rene’ Thomas formalism is applied in the study to generate a qualitative model which requires only the qualitative thresholds and associated logical parameters generated via SMBioNet software in accordance with biological observations. Furthermore, the continuous dynamics of the model have been studied via Petri nets based analysis. Results. In the presence of NS5A protein of HCV, the behaviors of the Natural Killer (NK) and T regulatory (Tregs) cells along with cytokines such as IFN-γ, IL-10, IL-12 are predicted. The model also attempts to consider the viral strategies to circumvent immune response mediated by viral proteins. The state graph analysis enabled the prediction of paths leading to disease state. The most probable cycle is predicted based on maximum betweenness centrality. Furthermore, to study the continuous dynamics of the modeled network, a Petri net (PN) model was generated. The predictive ability of the model implicates the critical role of IL-12 over-expression in pathogenesis. This observation speculates that IL-12 has a dual role under varying circumstances and leads to varying disease outcomes. Conclusion. This model attempts to reduce the noisy biological data and captures a holistic view of the regulations amongst the key determinants of HCV induced adaptive immune responses. The observations warrant for further studies to elucidate the role of IL-12 under varying external and internal stimuli. Also, introducing diversion by therapeutic perturbation may divert the system from diseased paths to recovery by stabilizing the activation of IFN-γ producing NK cells. The modeling approach employed in this study can be extended to include real-time experimental data to propose new therapeutic interventions.

scholarly journals Formal modeling of the key determinants of Hepatitis C Virus (HCV) induced adaptive immune response network: An integrative approach to map the cellular and cytokine-mediated host immune regulations

2018 ◽  
Author(s):  
Ayesha Obaid ◽  
Anam Naz ◽  
Shifa Tariq Ashraf ◽  
Faryal Mehwish Awan ◽  
Aqsa Ikram ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Immune System ◽  
Hepatitis C ◽  
Biological Data ◽  
Signaling Networks ◽  
Host Immune System ◽  
Adaptive Immune ◽  
Ifn Γ

Background. Hepatitis C Virus (HCV) is a major causative agent of liver infection leading to critical liver damage. In response to HCV, the improper regulation of host immune system leads to chronic infection. The host immune system employs multiple cell types, diverse variety of cytokine mediators and interacting signaling networks to neutralize the HCV infection. To understand the complexity of the interactions within the immune signaling networks, systems biology provides an efficient alternative approach. Integrating such approaches with immunology and virology helps to study highly complex immune regulatory networks within the host and presents a concise view of the whole system. Methods. Initially, a logic-based diagram is generated based on multiple reported interactions between immune cells and cytokines during host immune response to HCV. Furthermore, an abstracted sub-network is modeled qualitatively which consists of both the key cellular and cytokine components of the HCV induced immune system. Rene’ Thomas formalism is applied in the study to generate a qualitative model which requires only the qualitative thresholds and associated logical parameters generated via SMBioNet software in accordance with biological observations. Furthermore, the continuous dynamics of the model have been studied via Petri nets based analysis. Results. In the presence of NS5A protein of HCV, the behaviors of the Natural Killer (NK) and T regulatory (Tregs) cells along with cytokines such as IFN-γ, IL-10, IL-12 are predicted. The model also attempts to consider the viral strategies to circumvent immune response mediated by viral proteins. The state graph analysis enabled the prediction of paths leading to disease state. The most probable cycle is predicted based on maximum betweenness centrality. Furthermore, to study the continuous dynamics of the modeled network, a Petri net (PN) model was generated. The predictive ability of the model implicates the critical role of IL-12 over-expression in pathogenesis. This observation speculates that IL-12 has a dual role under varying circumstances and leads to varying disease outcomes. Conclusion. This model attempts to reduce the noisy biological data and captures a holistic view of the regulations amongst the key determinants of HCV induced adaptive immune responses. The observations warrant for further studies to elucidate the role of IL-12 under varying external and internal stimuli. Also, introducing diversion by therapeutic perturbation may divert the system from diseased paths to recovery by stabilizing the activation of IFN-γ producing NK cells. The modeling approach employed in this study can be extended to include real-time experimental data to propose new therapeutic interventions.

Role of the specific T‐cell response for clearance and control of hepatitis C virus

1999 ◽  
Vol 6 (s1) ◽  
pp. 36-40 ◽  
Author(s):  
G. R. Pape ◽  
T. J. Gerlach ◽  
H. M. Diepolder ◽  
N. Grüner ◽  
M.‐C. Jung ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
And Control

scholarly journals Nitric oxide production in murine spleen cells: role of interferons and prostaglandin E2in the generation of cytotoxic activity

1996 ◽  
Vol 5 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Dominique Vaillier ◽  
Richard Daculsi ◽  
Norbert Gualdel
Keyword(s):  
Nitric Oxide ◽  
Cytotoxic Activity ◽  
Minor Role ◽  
No Production ◽  
Spleen Cells ◽  
Kinase C ◽  
Murine Spleen ◽  
Ifn Γ ◽  
A Minor

The production of nitric oxide (NO) was measured in cultures of spleen cells stimulated by lipopolysaccharide (LPS), IL-2 or LPS + IL-2. We observed that NO synthesis is increased by IFN-γ but inhibited by IFN-α/β. This is not the case when IL-2 is present in the cultures, since interferons play a minor role in the regulation of the NO production. When IL-2 and LPS were associated in the cultures, the IFN-α/β role seems more important than that of IFN-γ. PGE2inhibits NO production in LPS supplemented cultures but has a slight effect in the presence of IL-2 and no effect with IL-2 + LPS. 3-isoButyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases, induces a decrease of IFN production. In the presence of H-7, an inhibitor of protein kinase C (PKC), NO production is reduced when the cultures are supplemented by LPS or IL-2 but not when IL-2 and LPS are both added. H-7 also reduced IFN production. In the presence of NG-monomethyl-L-arginine (N-MMA), an inhibitor of NO synthesis, IFN production was increased, with no change in the cytotoxic activity. Hence, interferons regulate NO production by mouse spleen cells and, in return, NO modulates the generation of IFN.

scholarly journals Control of Heterologous Hepatitis C Virus Infection in Chimpanzees Is Associated with the Quality of Vaccine-Induced Peripheral T-Helper Immune Response

2004 ◽  
Vol 78 (1) ◽  
pp. 187-196 ◽  
Author(s):  
C. Rollier ◽  
E. Depla ◽  
J. A. R. Drexhage ◽  
E. J. Verschoor ◽  
B. E. Verstrepen ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interleukin 2 ◽  
Hcv Infection ◽  
T Helper ◽  
Vaccine Strategy ◽  
Ns3 Protein ◽  
Ifn Γ

ABSTRACT Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, naïve chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the naïve infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-γ), protein-specific lymphoproliferative responses, IFN-γ, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection.

scholarly journals The Role of Micronutrients in the Infection and Subsequent Response to Hepatitis C Virus

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 603 ◽  
Author(s):  
Sunil Gupta ◽  
Scott A. Read ◽  
Nicholas A. Shackel ◽  
Lionel Hebbard ◽  
Jacob George ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Vitamin A ◽  
Innate Immune ◽  
Micronutrient Deficiencies ◽  
Strong Immune Response ◽  
Subsequent Response ◽  
Potent Immune Response

Micronutrient deficiencies develop for a variety of reasons, whether geographic, socioeconomic, nutritional, or as a result of disease pathologies such as chronic viral infection. As micronutrients are essential for a strong immune response, deficiencies can significantly dampen both the innate and the adaptive arms of antiviral immunity. The innate immune response in particular is crucial to protect against hepatitis C virus (HCV), a hepatotropic virus that maintains chronic infection in up to 80% of individuals if left untreated. While many micronutrients are required for HCV replication, an overlapping group of micronutrients are also necessary to enact a potent immune response. As the liver is responsible for the storage and metabolism of many micronutrients, HCV persistence can influence the micronutrients’ steady state to benefit viral persistence both directly and by weakening the antiviral response. This review will focus on common micronutrients such as zinc, iron, copper, selenium, vitamin A, vitamin B12, vitamin D and vitamin E. We will explore their role in the pathogenesis of HCV infection and in the response to antiviral therapy. While chronic hepatitis C virus infection drives deficiencies in micronutrients such as zinc, selenium, vitamin A and B12, it also stimulates copper and iron excess; these micronutrients influence antioxidant, inflammatory and immune responses to HCV.

scholarly journals Strategies to Circumvent Host Innate Immune Response by Hepatitis C Virus

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 274 ◽  
Author(s):  
Tapas Patra ◽  
Ratna Ray ◽  
Ranjit Ray
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Complement Activation ◽  
Cell Response ◽  
Nk Cell ◽  
Current Knowledge ◽  
Innate Immune ◽  
Spontaneous Clearance ◽  
Proinflammatory Response

Innate immune responses generate interferons, proinflammatory cytokines, complement activation, and natural killer (NK) cell response. Ultimately, this leads to the induction of a robust virus-specific adaptive immunity. Although the host innate immune system senses and responds to eliminate virus infection, hepatitis C virus (HCV) evades immune attack and establishes persistent infection within the liver. Spontaneous clearance of HCV infection is associated with a prompt induction of innate immunity generated in an infected host. In this review, we have highlighted the current knowledge of our understanding of host–HCV interactions, especially for endogenous interferon production, proinflammatory response, NK cell response, and complement activation, which may impair the generation of a strong adaptive immune response for establishment of chronicity. The information may provide novel strategies in augmenting therapeutic intervention against HCV.

scholarly journals Protective Role of Nitric Oxide inStaphylococcus aureus Infection in Mice

1998 ◽  
Vol 66 (3) ◽  
pp. 1017-1022 ◽  
Author(s):  
Sanae Sasaki ◽  
Tomisato Miura ◽  
Shinsuke Nishikawa ◽  
Kyogo Yamada ◽  
Mayuko Hirasue ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spleen Cell ◽  
Cell Cultures ◽  
Protective Role ◽  
Inos Mrna ◽  
No Production ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen cell cultures was induced by heat-killed S. aureus. Expression of mRNA of the inducible isoform of NO synthase (iNOS) was induced in the spleens and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF-α) or gamma interferon (IFN-γ) before S. aureus infection, the induction of iNOS mRNA expression in the kidneys was inhibited. These MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatment with aminoguanidine (AG), a selective inhibitor of iNOS. The survival rates of AG-treated mice were significantly decreased by either lethal or sublethal S. aureusinfections. However, an effect of AG administration on bacterial growth was not observed in the spleens and kidneys of mice during either type of infection. Production of TNF-α and IFN-γ was not affected by AG treatment in vitro and in vivo. These results suggest that NO plays an important role in protection from lethality by the infection, but the protective role of NO in host resistance against S. aureusinfection was not proved. Moreover, our results show that TNF-α and IFN-γ regulate NO production while NO may not be involved in the regulation of the production of these cytokines during S. aureus infection.

scholarly journals Role of Interferon-gamma and Immune Response Biomarkers in Predicting IFN-alpha Responsiveness and Treatment Outcome in Patients with Hepatitis C Virus

2012 ◽  
Vol 8 (4) ◽  
pp. 288-298 ◽  
Author(s):  
Amira F. Barakat ◽  
Asmaa Hegazy ◽  
Raghda E. Farag ◽  
Azza Abdul Baky ◽  
Lamiaa F. Arafa ◽  
...  
Keyword(s):  
Immune Response ◽  
Treatment Outcome ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Gamma ◽  
Ifn Alpha ◽  
Response Biomarkers
Sign in / Sign up

Export Citation Format

Share Document