scholarly journals Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests

2015 ◽  
Vol 8 ◽  
pp. IJTR.S26862 ◽  
Author(s):  
Vikram Mehraj ◽  
Jean-Pierre Routy
Keyword(s):  
Viral Infections ◽  
Acute Infection ◽  
Kynurenine Pathway ◽  
Therapeutic Interventions ◽  
Indoleamine 2 ◽  
Aryl Hydrocarbon ◽  
Chronic Viral Infections ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Tryptophan Catabolism

L-Tryptophan (L-Trp) is an essential amino acid that possesses diverse metabolic, neurological, and immunological roles spanning from the synthesis of proteins, neurotransmitter serotonin, and neurohormone melatonin, to its degradation into immunosuppressive catabolites by indoleamine-2, 3-dioxygenase (IDO) in the kynurenine pathway (KP). Trp catabolites, by activating aryl hydrocarbon receptor (AhR), play an important role in antimicrobial defense and immune regulation. IDO/AhR acts as a double-edged sword by both depleting L-Trp to starve the invaders and by contributing to the state of immunosuppression with microorganisms that were not cleared during acute infection. Pathogens experiencing Trp deprivation by IDO-mediated degradation include certain bacteria, parasites, and less likely viruses. However, chronic viral infections highjack the host immune response to create a state of disease tolerance via kynurenine catabolites. This review covers the latest data involving chronic viral infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes, and cytomegalovirus (CMV) and their cellular interplay with Trp catabolites. Strategies developed by viruses to escape immune control also represent new avenues for therapeutic interventions based on Trp metabolism.

scholarly journals CRISPR/Cas9-Based Antiviral Strategy: Current Status and the Potential Challenge

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1349 ◽  
Author(s):  
Choongho Lee
Keyword(s):  
Viral Infections ◽  
Adaptive Immune System ◽  
Virus Genome ◽  
General Concept ◽  
Current Status ◽  
Adaptive Immune ◽  
Chronic Viral Infections ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Potential Challenge

From its unexpected discovery as a bacterial adaptive immune system to its countless applications as one of the most versatile gene-editing tools, the CRISPR/Cas9 system has revolutionized every field of life science. Virology is no exception to this ever-growing list of CRISPR/Cas9-based applications. Direct manipulation of a virus genome by CRISPR/Cas9 has enabled a systematic study of cis-elements and trans-elements encoded in a virus genome. In addition, this virus genome-specific mutagenesis by CRISPR/Cas9 was further funneled into the development of a novel class of antiviral therapy targeting many incurable chronic viral infections. In this review, a general concept on the CRISPR/Cas9-based antiviral strategy will be described first. To understand the current status of the CRISPR/Cas9-based antiviral approach, a series of recently published antiviral studies involving CRISPR/Cas9-mediated control of several clinically-relevant viruses including human immunodeficiency virus, hepatitis B virus, herpesviruses, human papillomavirus, and other viruses will be presented. Lastly, the potential challenge and future prospect for successful clinical translation of this CRISPR/Cas9-based antiviral method will be discussed.

scholarly journals Frequency of Hepatitis B, C and HIV Infections among Transfusion-Dependent Beta Thalassemia Patients in Dhaka

2021 ◽  
Vol 13 (1) ◽  
pp. 89-95
Author(s):  
Golam Sarower Bhuyan ◽  
Aftab Uz Zaman Noor ◽  
Rosy Sultana ◽  
Farjana Akther Noor ◽  
Nusrat Sultana ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Viral Infections ◽  
Rapid Test ◽  
Hiv Infections ◽  
Beta Thalassemia ◽  
Nucleic Acid Testing ◽  
Serological Testing ◽  
Elisa Method ◽  
B Virus ◽  
Immunodeficiency Virus

Transfusion transmitted infections have remained a major deterrent to public health, particularly among the patients with transfusion-dependent Beta thalassemia in developing countries. Although proper donor selection through adoption of WHO-advised infection panel has lowered the rate of infections, the multi-transfused patients are not free of risk. In this study, we screened 148 transfusion-dependent Beta thalassemia patients to determine the frequency of Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) using the ELISA method. Among them, infected cases with HCV, HBV and HIV were 13.51%, 3.37% and 0%, respectively. Moreover, 2% of the patients were found to be co-infected with both HBV and HCV. The percentage of infections in the patients with frequent transfusion interval (≤30 days) was significantly higher (p < 0.0005) than that in the patients with less frequent transfusion intervals (>30 days). Immunochromatography (ICT)-based rapid test kits are usually used to screen and confirm these infections in the blood of the patients. However, ICT-based tests are not sensitive enough to detect the infections. So, a combination of both Nucleic Acid testing (NAT) and serological testing are suggested to significantly reduce the risk of viral infections during blood transfusion.

scholarly journals Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice

2016 ◽  
Vol 90 (19) ◽  
pp. 8563-8574 ◽  
Author(s):  
Marianna Di Scala ◽  
Itziar Otano ◽  
Irene Gil-Fariña ◽  
Lucia Vanrell ◽  
Mirja Hommel ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Chronic Hepatitis B ◽  
Viral Infections ◽  
Chronic Viral Infections ◽  
B Virus ◽  
Interleukin 15

ABSTRACTIn chronic hepatitis B (CHB), failure to control hepatitis B virus (HBV) is associated with T cell dysfunction. HBV transgenic mice mirror many features of the human disease, including T cell unresponsiveness, and thus represent an appropriate model in which to test novel therapeutic strategies. To date, the tolerant state of CD8+T cells in these animals could be altered only by strong immunogens or by immunization with HBV antigen-pulsed dendritic cells; however, the effectors induced were unable to suppress viral gene expression or replication. Because of the known stimulatory properties of alpha interferon (IFN-α) and interleukin-15 (IL-15), this study explored the therapeutic potential of liver-directed gene transfer of these cytokines in a murine model of CHB using adeno-associated virus (AAV) delivery. This combination not only resulted in a reduction in the viral load in the liver and the induction of an antibody response but also gave rise to functional and specific CD8+immunity. Furthermore, when splenic and intrahepatic lymphocytes from IFN-α- and IL-15-treated animals were transferred to new HBV carriers, partial antiviral immunity was achieved. In contrast to previous observations made using either cytokine alone, markedly attenuated PD-L1 induction in hepatic tissue was observed upon coadministration. An initial study with CHB patient samples also gave promising results. Hence, we demonstrated synergy between two stimulating cytokines, IL-15 and IFN-α, which, given together, constitute a potent approach to significantly enhance the CD8+T cell response in a state of immune hyporesponsiveness. Such an approach may be useful for treating chronic viral infections and neoplastic conditions.IMPORTANCEWith 350 million people affected worldwide and 600,000 annual deaths due to HBV-induced liver cirrhosis and/or hepatocellular carcinoma, chronic hepatitis B (CHB) is a major health problem. However, current treatment options are costly and not very effective and/or need to be administered for life. The unprecedented efficacy of the strategy described in our paper may offer an alternative and is relevant for a broad spectrum of readers because of its clear translational importance to other chronic viral infections in which a hyporesponsive antigen-specific T cell repertoire prevents clearance of the pathogen.

scholarly journals Usefulness of Simultaneous Screening for HIV- and Hepatitis C–Specific Antibodies and Hepatitis B Surface Antigen by Capillary-Based Multiplex Immunochromatographic Rapid Test to Strengthen Prevention Strategies and Linkage to Care in Childbearing-Aged Women Living in Resource-Limited Settings

2018 ◽  
Vol 5 (5) ◽  
Author(s):  
Ralph-Sydney Mboumba Bouassa ◽  
Zita Aleyo Nodjikouambaye ◽  
Damtheou Sadjoli ◽  
Ali Mahamat Moussa ◽  
Chatte Adawaye ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Viral Infections ◽  
Hepatitis B Surface Antigen ◽  
Rapid Test ◽  
Linkage To Care ◽  
Chronic Viral Infections ◽  
Resource Limited ◽  
B Virus

Abstract Childbearing-aged women (n = 266) attending a gynecological clinic in Chad were subjected to multiplex immunochromatographic rapid test for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). Ten (3.7%) and 8 (3.0%) were seropositive for HIV and HCV, respectively, and 20 (7.5%) for HBV surface antigen, allowing diagnosis of chronic viral infections in 1 of 7 (14.3%) women.

Prevention of Infection-Related Cancers

2017 ◽  
Author(s):  
Marc Bulterys ◽  
Julia Brotherton ◽  
Ding-Shinn Chen
Keyword(s):  
Randomized Clinical Trials ◽  
Viral Infections ◽  
Prevention Measures ◽  
Barr Virus ◽  
Non Hodgkin Lymphoma ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr ◽  
Liver Flukes

This chapter discusses primary prevention measures that disrupt transmission of oncogenic infections. It begins by discussing vaccination against hepatitis B virus (HBV) and human papillomavirus (HPV), two major causes of cancer for which safe and effective vaccines are currently available. It briefly discusses the importance of treatment and prophylaxis against human immunodeficiency virus type 1 (HIV-1), which potentiates the virulence of other viral infections as well as directly increasing the incidence of non-Hodgkin lymphoma. It does not discuss the treatment of HBV or hepatitis C virus (HCV) infection, since these are considered in Chapters 25 and 33. Also beyond the scope of this chapter are the randomized clinical trials currently underway to assess the efficacy and feasibility of eradication of Helicobacter pylori (Chapters 24, 31), vaccination against Epstein-Barr virus (EBV) (Chapters 24, 26, 39), or the prevention of schistosomiasis and liver flukes (Chapters 24, 33, and 52).

scholarly journals Loss of Resistance to Mousepox during Chronic Lymphocytic Choriomeningitis Virus Infection Is Associated with Impaired T-Cell Responses and Can Be Rescued by Immunization

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Pedro Alves-Peixoto ◽  
Maria Férez ◽  
Cory J. Knudson ◽  
Carolina R. Melo-Silva ◽  
Colby Stotesbury ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Infection ◽  
Viral Infections ◽  
Acute Infection ◽  
T Cell Responses ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
T Cell Response ◽  
Cell Responses ◽  
Chronic Viral Infections

ABSTRACT It is well established that chronic viral infections can cause immune suppression, resulting in increased susceptibility to other infectious diseases. However, the effects of chronic viral infection on T-cell responses and vaccination against highly pathogenic viruses are not well understood. We have recently shown that C57BL/6 (B6) mice lose their natural resistance to wild-type (WT) ectromelia virus (ECTV) when chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13). Here we compared the T-cell response to ECTV in previously immunologically naive mice that were chronically infected with CL13 or that were convalescent from acute infection with the Armstrong (Arm) strain of LCMV. Our results show that mice that were chronically infected with CL13 but not those that had recovered from Arm infection have highly defective ECTV-specific CD8+ and CD4+ T-cell responses to WT ECTV. These defects are at least partly due to the chronic infection environment. In contrast to mice infected with WT ECTV, mice chronically infected with CL13 survived without signs of disease when infected with ECTV-Δ036, a mutant ECTV strain that is highly attenuated. Strikingly, mice chronically infected with CL13 mounted a strong CD8+ T-cell response to ECTV-Δ036 and survived without signs of disease after a subsequent challenge with WT ECTV. Our work suggests that enhanced susceptibility to acute viral infections in chronically infected individuals can be partly due to poor T-cell responses but that sufficient T-cell function can be recovered and resistance to acute infection can be restored by immunization with highly attenuated vaccines. IMPORTANCE Chronic viral infections may result in immunosuppression and enhanced susceptibility to infections with other pathogens. For example, we have recently shown that mice chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) are highly susceptible to mousepox, a disease that is caused by ectromelia virus and that is the mouse homolog of human smallpox. Here we show chronic CL13 infection severely disrupts the expansion, proliferation, activation, and cytotoxicity of T cells in response due at least in part to the suppressive effects of the chronic infection milieu. Notably, despite this profound immunodeficiency, mice chronically infected with CL13 could be protected by vaccination with a highly attenuated variant of ECTV. These results demonstrate that protective vaccination of immunosuppressed individuals is possible, provided that proper immunization tools are used.

VIRUS INACTIVATION AND COAGULATION FACTOR PREPARATIONS

1987 ◽  
Author(s):  
B L Evatt
Keyword(s):  
Hepatitis B ◽  
Hemophilia A ◽  
Viral Infections ◽  
Coagulation Factor ◽  
Viral Inactivation ◽  
Large Numbers ◽  
Heat Treated ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Hemophilia Treatment Centers

Nonheat-treated factor concentrates were used for the therapy of congenital and acquired coagulation deficiencies until 1984. These unheated factor crticentrates, which are manufactured from pooled plasma obtained from between 2500 and 25,000 blood or plasma donors, have been epidemiologically implicated in exposure of large numbers of hemophilia patients to several viral infections Including human immunodeficiency virus (HIV), hepatitis B, and non-A non-B hepatitis. Of these, HIV has been fdund to be very heat labile. After the introduction in 1984-85 of heat treatment of concentrates to reduce the risk of! hepatitis to recipients, several studies documented a lack of HIV serconversion in patients treated with clotting-fadtor concentrates. However, subsequent reports described a few hemophilia patients who had seroconverted to HIV! after receiving heat-treated concentrate from unscreened donors. To determine the significance of these seroconvers(ions, an international survey was conducted on 11 hemophilia treatment centers in Europe, Canada, and the United Kingdcpn whose total patient population comprised more than 2300 hemophilia A patients and 400 hemophilia B patients. Only three patients were found who seroconverted beyond a 6-month period after switching to heat-treated material, a(nd no seroconversions have occurred in these centers between November 1985 and February 1987. In addition no cases of seroconversion on donor screened heat-treated concentrate have been reported since its widespread introduction to the hemophilia patients during 1985-1986. Other modes of viral inactivation are currently being tested, and they appeiar to be effective in inactivating HIV and hepatitis B virus. Some of these methods have shown some promise for the inactivation of non-A and non-B hepatitis, but more data are needed for final assessment of these methods.

scholarly journals Chronic microbial infections: Manipulation of host immunity as interventional approach

1970 ◽  
Vol 1 (1) ◽  
pp. 13-19
Author(s):  
Sheikh Mohammad Fazle Akbar ◽  
Md Sakirul Islam Khan ◽  
Shunji Mishiro
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Acute Infection ◽  
Immune Surveillance ◽  
Host Immune System ◽  
Related Factors ◽  
Chronic Viral Infections ◽  
Microbial Infections

Chronic viral infections represent major challenges in contemporary medicine, virology and pharmacology. The virus-bearing hosts are commonly found in every parts of the world and it is extremely difficult to manage these patients. In addition, considerable numbers of these patients develop progressive diseases and severe complications. Finally, most of these patients act as permanent reservoirs of virus. Understandings of viral life cycle during the last decade of 20th century and the first decade of 21st century have allowed development of hundreds of antiviral agents for different diseases. But, the clinical efficacy of these drugs is not yet satisfactory. In addition, virologists have provided conclusive evidences suggesting that eradication of most chronic virus from infected hosts may an unachievable goal. In this context, it is essential to develop alternative, novel, and evidence-based therapeutic maneuver for these patients. Manipulation of host immune system may be one of these approaches. We would discuss about scopes, limitations, and strategies for manipulation for controlling of chronic viral infections. The primary function of the host's immune system is to mount responses that protect the individual from various microbial infections including viruses. Host's immune responses also control the spread and virulence of the viruses [1]. This is applicable to viruses that cause acute infection. After entering the hosts, these viruses are localized in host's tissues, proliferate and induce antiviral immunity. These cellular events may cause damage and destruction of tissues and the host exhibit features of acute inflammatory diseases. However, the viruses are either almost completely eliminated from the hosts or adequately controlled in situ by host's immune systems. However, chronic infection is established by many viruses because the hosts induce improper and uncoordinated immune responses against these viruses. Most viruses cause persistent infection by evading the host immune surveillance mechanism. Both virus-related factors and host-dependent factors are primarily responsible for viral persistency in subjects with chronic viral infections.    doi: 10.3329/blj.v1i1.2620 Bangladesh Liver Journal Vol.1(1) 2009 p.13-19 

scholarly journals Does Interleukin-6 Bridge SARS-CoV-2 With Virus-Associated Cancers?

2021 ◽  
Author(s):  
Aldo Venuti ◽  
Sara Donzelli ◽  
Paola Nisticò ◽  
Giovanni Blandino ◽  
Gennaro Ciliberto
Keyword(s):  
Interleukin 6 ◽  
Viral Infections ◽  
Critical Role ◽  
Direct Interaction ◽  
Molecular Profile ◽  
Populations At Risk ◽  
Selective Targeting ◽  
B Virus ◽  
Immunodeficiency Virus

ABSTRACT To date SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a member of the Coronaviridae family, has infected more than 40 million people worldwide. A second wave of SARS-CoV-2 infection is aggressively surging. The clinical worsening of SARS-CoV-2 infection appears to be strictly associated with comorbidities, which can be used to establish an intrinsic patient network whose molecular profile is pivotal for identifying and successfully treating populations at risk. Herein, we focus on the direct interaction between SARS-CoV-2 and virus-associated cancers, exploring the critical role of interleukin-6 (IL-6) as a mediator of this complex cross talk. IL-6 production is enhanced in diverse viral infections ranging from human papilloma virus (HPV) to hepatitis B virus (HBV), human immunodeficiency virus (HIV), and SARS-CoV-2 infection. High systemic levels of IL-6 are associated with viral persistence and poor clinical outcomes in SARS-CoV-2–infected patients. Blockade of IL-6/IL-6R, using specific molecules, is under investigation in active clinical trials for the treatment of patients with SARS-CoV-2. Although the data are as yet inconclusive, they pave the way for selective targeting of crucial cytokine-activated aberrant signaling in SARS-CoV-2 infection.

scholarly journals Inhibition of Reverse Transcriptase as A Clue for Curing RNA Viral Infections

2020 ◽  
Vol 5 (6) ◽  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Viral Infections ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Plausible Mechanism ◽  
Hiv 1

Scientists provide evidence showing that delayed chain discontinuation is a plausible mechanism of action of Remdesivir. This mechanism was described previously in the context of reverse transcriptase (RT) inhibition of human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus

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