scholarly journals Effects of APOBEC3G's Cytidine Deaminase Activity on Retroviral Evolution

2021 ◽  
Vol 15 ◽  
pp. 55-61
Author(s):  
Mary-Benedicta Obikili
Keyword(s):  
Viral Infection ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Cytidine Deaminase ◽  
Viral Evolution ◽  
Cytidine Deaminase Activity ◽  
Immunodeficiency Virus ◽  
Potential Impact ◽  
Retroviral Infections

Apolipoprotein B editing complex (APOBEC3/A3) genes are found in mammalian cells. In primates, there are 7 APOBEC3 genes, namely, 3A, 3B, 3C, 3DE, 3F, 3G, and 3H. Previous research has shown that A3 proteins help to inhibit viral infection via their cytidine deaminase activity. However, it has also been found that A3 proteins could also lead to viral evolution, where viruses such as HIV (Human Immunodeficiency Virus) instead gain beneficial mutations that enable them to overcome the antiviral activity of A3 proteins, gain resistance to certain drugs used for treating viral infections and escape recognition by the immune system. This paper is a review article summarizing the role of A3G on viral infection and evolution, and the potential impact viral evolution could have in treatment of retroviral infections such as HIV.

scholarly journals HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1102
Author(s):  
Nicholas A. Mathieu ◽  
Ermela Paparisto ◽  
Stephen D. Barr ◽  
Donald E. Spratt
Keyword(s):  
Mammalian Cells ◽  
Drug Targets ◽  
Influenza A ◽  
Viral Infections ◽  
Viral Proteins ◽  
Viral Pathogens ◽  
Antiviral Immune Response ◽  
Immunodeficiency Virus ◽  
Interferon Stimulated Gene 15

Mammalian cells have developed an elaborate network of immunoproteins that serve to identify and combat viral pathogens. Interferon-stimulated gene 15 (ISG15) is a 15.2 kDa tandem ubiquitin-like protein (UBL) that is used by specific E1–E2–E3 ubiquitin cascade enzymes to interfere with the activity of viral proteins. Recent biochemical studies have demonstrated how the E3 ligase HECT and RCC1-containing protein 5 (HERC5) regulates ISG15 signaling in response to hepatitis C (HCV), influenza-A (IAV), human immunodeficiency virus (HIV), SARS-CoV-2 and other viral infections. Taken together, the potent antiviral activity displayed by HERC5 and ISG15 make them promising drug targets for the development of novel antiviral therapeutics that can augment the host antiviral response. In this review, we examine the emerging role of ISG15 in antiviral immunity with a particular focus on how HERC5 orchestrates the specific and timely ISGylation of viral proteins in response to infection.

Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic Interplay Involving All Phases of the Viral Life Cycle

2018 ◽  
Vol 16 (3) ◽  
pp. 184-207 ◽  
Author(s):  
Vanessa D`Urbano ◽  
Elisa De Crignis ◽  
Maria Carla Re
Keyword(s):  
Mammalian Cells ◽  
Viral Evolution ◽  
Type I ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Immunodeficiency Virus ◽  
Lentiviral Infection ◽  
Specific Proteins ◽  
Hiv 1

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus. The identification and characterization of RFs have provided unique insights into the molecular biology of HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection. The presence of RFs drove viral evolution, forcing the virus to develop specific proteins to counteract their activity. The knowledge of the mechanisms that prevent viral infection and their viral counterparts may offer new insights to improve current antiviral strategies. This review provides an overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expression as well as their impact on viral replication and the clinical course of the disease.

scholarly journals PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

scholarly journals Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1200 ◽  
Author(s):  
Allen Caobi ◽  
Madhavan Nair ◽  
Andrea D. Raymond
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Membrane Vesicles ◽  
Response Modulation ◽  
Viral Spread ◽  
Neurotropic Viruses ◽  
Immunodeficiency Virus ◽  
Immune Response Modulation ◽  
Potential Use

Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review’s scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.

scholarly journals Preexisting Virus-Specific T Lymphocytes-Mediated Enhancement of Adenovirus Infections to Human Blood CD14+ Cells

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 154
Author(s):  
Fengling Feng ◽  
Jin Zhao ◽  
Pingchao Li ◽  
Ruiting Li ◽  
Ling Chen ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Viral Infection ◽  
Viral Infections ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Activation Markers ◽  
Gm Csf ◽  
Cell Responses ◽  
Underlying Mechanisms

Antigen-specific T lymphocytes play a critical role in controlling viral infections. However, we report here that preexisting virus-specific T cell responses also contribute to promoting adenovirus (Ad) infection. Previously, we found that CD14+ monocytes from Ad-seropositive individuals exhibited an increased susceptibility to Ad infection, when compared with that of Ad-seronegative individuals. But the underlying mechanisms for this enhancement of viral infection are not completely clarified. In this study, we found that the efficacy of Ad infection into CD14+ monocytes was significantly decreased after CD3+ T lymphocytes depletion from PBMC samples of Ad-seropositive individuals. In contrast, adding virus-specific CD3+ T lymphocytes into PBMC samples of Ad-seronegative individuals resulted in a significant increase of infection efficacy. CD3+ T lymphocytes in PBMC samples from Ad-seropositive individuals were more sensitive to be activated by adenovirus stimulus, characterized by upregulation of multiple cytokines and activation markers and also enhancement of cell proliferation. Further studies demonstrated that GM-CSF and IL-4 can promote Ad infection by up-regulating the expression of scavenger receptor 1 (SR-A) and integrins αVβ5 receptor of CD14+ cells. And taken together, these results suggest a novel role of virus-specific T cells in mediating enhancement of viral infection, and provide insights to understand the pathogenesis and complicated interactions between viruses and host immune cells.

scholarly journals Dengue Virus and the Relationship with MicroRNAs

2020 ◽  
Author(s):  
Samir Casseb ◽  
Karla de Melo
Keyword(s):  
Dengue Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Defense ◽  
Tropical Regions ◽  
Denv Serotypes ◽  
History Of ◽  
Infection Processes ◽  
The Relationship

Dengue is an acute febrile disease caused by a virus of the genus Flavivirus, family Flaviviridae, endemic in tropical regions of the globe. The agent is a virus with single-stranded RNA, classified into four distinct dengue virus (DENV) serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The host’s innate and adaptive immune responses play an essential role in determining the natural history of viral infections, especially in dengue. In this context, it has observed in recent years that the presence of RNA interference (RNAi) in viral infection processes is increasing, as well as immune defense. The context microRNAs (miRNAs) go for stood out, as their presence during viral infection, both in the replication of the virus and in the defense against these infections, becomes increasingly noticeable, therefore, making it increasingly necessary to better understand the role of these small RNAs within viral infection by DENV and what their consequences are in aggravating the consequences of patients affected by this disease.

scholarly journals BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection

2020 ◽  
pp. jcs.251835
Author(s):  
Azia S. Evans ◽  
Nicholas J. Lennemann ◽  
Carolyn B. Coyne
Keyword(s):  
Mass Spectrometry ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Rna Viruses ◽  
Rna Virus ◽  
Negative Regulator ◽  
Host Factors ◽  
Important Negative Regulator ◽  
Cellular Components

Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique methods for avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses and flaviviruses, usurp the autophagic pathway to promote their own replication. We previously identified the endoplasmic reticulum-localized protein BPIFB3 as an important negative regulator of non-canonical autophagy that uniquely impacts the replication of enteroviruses and flaviviruses. Here, we find that many components of the canonical autophagy machinery are not required for BPIFB3 depletion induced autophagy and identify the host factors that facilitate its role in the replication of enteroviruses and flaviviruses. Using proximity-dependent biotinylation (BioID) followed by mass spectrometry, we identify ARFGAP1 and TMED9 as two cellular components that interact with BPIFB3 to regulate autophagy and viral replication. Importantly, our data demonstrate that non-canonical autophagy in mammalian cells can be controlled outside of the traditional pathway regulators and define the role of two proteins in BPIFB3 depletion mediated non-canonical autophagy.

scholarly journals Antioxidant Treatment Reduces Expansion and Contraction of Antigen-Specific CD8+ T Cells during Primary but Not Secondary Viral Infection

2004 ◽  
Vol 78 (20) ◽  
pp. 11246-11257 ◽  
Author(s):  
Nathan G. Laniewski ◽  
Jason M. Grayson
Keyword(s):  
T Cells ◽  
Viral Infection ◽  
Large Scale ◽  
Viral Infections ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Response ◽  
Oxygen Intermediates ◽  
Mimetic Compound

ABSTRACT During many viral infections, antigen-specific CD8+ T cells undergo large-scale expansion. After viral clearance, the vast majority of effector CD8+ T cells undergo apoptosis. Previous studies have implicated reactive oxygen intermediates (ROI) in lymphocyte apoptosis. The purpose of the experiments presented here was to determine the role of ROI in the expansion and contraction of CD8+ T cells in vivo during a physiological response such as viral infection. Mice were infected with lymphocytic choriomeningitis virus (LCMV) and treated with Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a metalloporphyrin-mimetic compound with superoxide dismutase activity, from days 0 to 8 postinfection. At the peak of CD8+-T-cell response, on day 8 postinfection, the numbers of antigen-specific cells were 10-fold lower in MnTBAP-treated mice than in control mice. From days 8 to 30, a contraction phase ensued where the numbers of antigen-specific CD8+ T cells declined 25-fold in vehicle-treated mice compared to a 3.5-fold decrease in MnTBAP-treated mice. Differences in contraction appeared to be due to greater proliferation in drug-treated mice. By day 38, the numbers of antigen-specific CD8+ memory T cells were equivalent for the two groups. The administration of MnTBAP during secondary viral infection had no effect on the expansion of antigen-specific CD8+ secondary effector T cells. These data suggest that ROI production is critical for the massive expansion and contraction of antigen-specific CD8+ T cells during primary, but not secondary, viral infection.

scholarly journals RdDM pathway is required for Tobamovirus-induced symptomatology production

2020 ◽  
Author(s):  
Melisa Leone ◽  
Diego Zavallo ◽  
Andrea Venturuzzi ◽  
Sebastián Asurmendi
Keyword(s):  
Dna Methylation ◽  
Viral Infection ◽  
Viral Infections ◽  
Expression Patterns ◽  
Initial Step ◽  
List Type ◽  
Direct Role ◽  
Transcriptional Changes ◽  
Virus Interactions

SummarySmall RNAs (sRNA) are important molecules for gene regulation in plants and play an essential role in plant-pathogen interactions. Researchers have evaluated the relationship between viral infections as well as the endogenous accumulation of sRNAs and the transcriptional changes associated with the production of symptoms, little is known about a possible direct role of epigenetics, mediated by 24-nt sRNAs, in the induction of these symptoms.With the use of different RNA directed DNA methylation pathway mutants and triple demethylase mutants, here we demonstrate that the disruption of RdDM pathway during viral infection produced alterations in the plant transcriptomic changes (because of the infection) and in symptomatology.This study represents the initial step in exposing that DNA methylation directed by endogenous sRNAs has an important role, uncoupled to defense, in the production of symptoms associated with plant-virus interactions.Significance statementThe crop yield losses induced by phytoviruses are mainly associated with the symptoms of the disease. DNA modifications as methylation, can modulate the information coded by the sequence, process named epigenetics. Viral infection can change the expression patterns of different genes linked to defenses and symptoms. This work represents the initial step to expose the role of epigenetic process, in the production of symptoms associated with plants-virus interactions.

scholarly journals United States Ending the Human Immunodeficiency Virus (HIV) Epidemic plan: evaluation of the role of industry funding in published pre-exposure prophylaxis (PrEP) literature

2021 ◽  
Author(s):  
Somya Gupta ◽  
Reuben Granich
Keyword(s):  
Industry Funding ◽  
Potential Conflict ◽  
Immunodeficiency Virus ◽  
The Us ◽  
Frequent Testing ◽  
Potential Impact ◽  
Corporate Support ◽  
Exposure Prophylaxis ◽  
The Impact

Pre-exposure prophylaxis (PrEP) is integral to the US End of AIDS strategy. However, low adherence, high costs, frequent testing and monitoring side effects make delivery of PrEP complicated. Gilead has sponsored PrEP-related research efforts and access as part of its marketing efforts. We review potential conflict of interests (COI) in the scientific literature for the US PrEP related articles to understand the impact of Gilead’s corporate sponsorship.We identified 93 US PrEP articles published in the top 10 medical journals and top 10 HIV/AIDS journals in 2018. There were 289 first three and senior authors in these articles, of which, 34 (11%) declared a Gilead COI and 28 (10%) had undeclared Gilead COI. Only 10 authors accounted for 50% of the articles, with 70% of them having potential COI including receiving grants, fees and study drugs. The 93 articles were associated with 51 leading institutions (institution of three or more authors or participating institutions in a trial). Authors from 12 (24%) institutions declared an institutional Gilead COI and 22 (45%) institutions had undeclared Gilead support. Overall, of the 93 included articles, 30 (32%) had declared Gilead COI. Combining declared and undeclared COIs for authors and institutions provided an overall 83 (89%) articles with a potential Gilead COI. Of the 93 articles, 60 (71%) had favorable conclusions in 60 (71%). Declared Gilead support was significantly associated with favorable article conclusions (p<.05) but combined declared/undeclared author and/or institutional Gilead support was not associated with favorable conclusion. Nearly 90% of US PrEP articles had Gilead support and authors failed to report individual or institutional COI in 70% of articles. Direct corporate support is important for scientific research. However, Gilead’s marketing push for PrEP, undeclared COI, and potential influence of Gilead supported authors are of concern given the potential impact on the scientific discourse and the US HIV control strategy.

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