Apoptosis and autophagy as a turning point in viral–host interactions: the case of human norovirus and its surrogates

2020 ◽  
Author(s):  
Sean Kennedy ◽  
Mélanie M Leroux ◽  
Alexis Simons ◽  
Brice Malve ◽  
Marc Devocelle ◽  
...  
Keyword(s):  
Viral Entry ◽  
Turning Point ◽  
Infection Process ◽  
Host Interactions ◽  
Antiviral Therapies ◽  
Leading Role ◽  
Host Interaction ◽  
Major Response ◽  
Causes Of Disease ◽  
Viral Host Interactions

Human gastroenteritis viruses are amid the major causes of disease worldwide, responsible for more than 2 million deaths per year. Human noroviruses play a leading role in the gastroenteritis outbreaks and the continuous emergence of new strains contributes to the significant morbidity and mortality. Many aspects of the viral entry and infection process remain unclear, including the major response of the host cell to the virus, which is the trigger of several programmed cell death related mechanisms. In this review, we assessed apoptosis and autophagy at various stages in the infection process to provide better understanding of the viral–host interaction. This brings us closer to fully understanding how noroviruses work, thus allowing the development of specific antiviral therapies.

scholarly journals Potential Use of CRISPR/Cas13 Machinery in Understanding Virus–Host Interaction

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmoud Bayoumi ◽  
Muhammad Munir
Keyword(s):  
Degradation Process ◽  
Host Interactions ◽  
Host Interaction ◽  
Evolutionary Features ◽  
Subsequent Degradation ◽  
Viral Host Interactions ◽  
Target Rna ◽  
Potential Use ◽  
Specific Sequences ◽  
Cas Proteins

Prokaryotes have evolutionarily acquired an immune system to fend off invading mobile genetic elements, including viral phages and plasmids. Through recognizing specific sequences of the invading nucleic acid, prokaryotes mediate a subsequent degradation process collectively referred to as the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)–CRISPR-associated (Cas) (CRISPR–Cas) system. The CRISPR–Cas systems are divided into two main classes depending on the structure of the effector Cas proteins. Class I systems have effector modules consisting of multiple proteins, while class II systems have a single multidomain effector. Additionally, the CRISPR–Cas systems can also be categorized into types depending on the spacer acquisition components and their evolutionary features, namely, types I–VI. Among CRISPR/Cas systems, Cas9 is one of the most common multidomain nucleases that identify, degrade, and modulate DNA. Importantly, variants of Cas proteins have recently been found to target RNA, especially the single-effector Cas13 nucleases. The Cas13 has revolutionized our ability to study and perturb RNAs in endogenous microenvironments. The Cas13 effectors offer an excellent candidate for developing novel research tools in virological and biotechnological fields. Herein, in this review, we aim to provide a comprehensive summary of the recent advances of Cas13s for targeting viral RNA for either RNA-mediated degradation or CRISPR–Cas13-based diagnostics. Additionally, we aim to provide an overview of the proposed applications that could revolutionize our understanding of viral–host interactions using Cas13-mediated approaches.

scholarly journals Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 448
Author(s):  
Sineewanlaya Wichit ◽  
Nuttamonpat Gumpangseth ◽  
Rodolphe Hamel ◽  
Sakda Yainoy ◽  
Siwaret Arikit ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Virus Transmission ◽  
Antiviral Agent ◽  
Viral Proteins ◽  
Targeted Therapeutics ◽  
Limited Information ◽  
Mosquito Vectors ◽  
Host Proteins ◽  
Host Interactions ◽  
Viral Host Interactions

Chikungunya and Zika viruses, both transmitted by mosquito vectors, have globally re-emerged over for the last 60 years and resulted in crucial social and economic concerns. Presently, there is no specific antiviral agent or vaccine against these debilitating viruses. Understanding viral–host interactions is needed to develop targeted therapeutics. However, there is presently limited information in this area. In this review, we start with the updated virology and replication cycle of each virus. Transmission by similar mosquito vectors, frequent co-circulation, and occurrence of co-infection are summarized. Finally, the targeted host proteins/factors used by the viruses are discussed. There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses.

scholarly journals The key amino acids of E protein involved in early flavivirus infection: viral entry

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tao Hu ◽  
Zhen Wu ◽  
Shaoxiong Wu ◽  
Shun Chen ◽  
Anchun Cheng
Keyword(s):  
Amino Acids ◽  
Conformational Changes ◽  
Viral Entry ◽  
Envelope Protein ◽  
Cell Attachment ◽  
Envelope Proteins ◽  
Infection Process ◽  
Early Infection ◽  
Protein Amino Acids ◽  
Α Helix

AbstractFlaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.

scholarly journals Apicortin, a Constituent of Apicomplexan Conoid/Apical Complex and Its Tentative Role in Pathogen—Host Interaction

2021 ◽  
Vol 6 (3) ◽  
pp. 118
Author(s):  
Ferenc Orosz
Keyword(s):  
Plasmodium Falciparum ◽  
Toxoplasma Gondii ◽  
Therapeutic Target ◽  
In Silico ◽  
Free Living ◽  
Binding Properties ◽  
Host Interactions ◽  
Trichoplax Adhaerens ◽  
Host Interaction ◽  
Apical Complex

In 2009, apicortin was identified in silico as a characteristic protein of apicomplexans that also occurs in the placozoa, Trichoplax adhaerens. Since then, it has been found that apicortin also occurs in free-living cousins of apicomplexans (chromerids) and in flagellated fungi. It contains a partial p25-α domain and a doublecortin (DCX) domain, both of which have tubulin/microtubule binding properties. Apicortin has been studied experimentally in two very important apicomplexan pathogens, Toxoplasma gondii and Plasmodium falciparum. It is localized in the apical complex in both parasites. In T. gondii, apicortin plays a key role in shaping the structure of a special tubulin polymer, conoid. In both parasites, its absence or downregulation has been shown to impair pathogen–host interactions. Based on these facts, it has been suggested as a therapeutic target for treatment of malaria and toxoplasmosis.

scholarly journals TRPC1 participates in the HSV-1 infection process by facilitating viral entry

2020 ◽  
Vol 6 (12) ◽  
pp. eaaz3367 ◽  
Author(s):  
DongXu He ◽  
AiQin Mao ◽  
YouRan Li ◽  
SiuCheung Tam ◽  
YongTang Zheng ◽  
...  
Keyword(s):  
Viral Entry ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Critical Role ◽  
Receptor Potential ◽  
Infection Process ◽  
Ocular Abnormality ◽  
Simplex Virus ◽  
Hsv 1

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1–induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1–induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1–infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.

Hepatitis B virus: from immunobiology to immunotherapy

2012 ◽  
Vol 124 (2) ◽  
pp. 77-85 ◽  
Author(s):  
Daniel Grimm ◽  
Maximilian Heeg ◽  
Robert Thimme
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Therapeutic Approaches ◽  
Major Health ◽  
Antiviral Therapies ◽  
Adaptive Immune ◽  
Host Interaction ◽  
Current State ◽  
B Virus ◽  
Chronic Hbv

Owing to the major limitations of current antiviral therapies in HBV (hepatitis B virus) infection, there is a strong need for novel therapeutic approaches to this major health burden. Stimulation of the host's innate and adaptive immune responses in a way that results in the resolution of viral infection is a promising approach. A better understanding of the virus–host interaction in acute and chronic HBV infection revealed several possible novel targets for antiviral immunotherapy. In the present review, we will discuss the current state of the art in HBV immunology and illustrate how control of infection could be achieved by immunotherapeutic interventions.

scholarly journals Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 30 ◽  
Author(s):  
Jason Long ◽  
Edward Wright ◽  
Eleonora Molesti ◽  
Nigel Temperton ◽  
Wendy Barclay
Keyword(s):  
Viral Entry ◽  
Intervention Strategies ◽  
Marburg Virus ◽  
Viral Diseases ◽  
Antiviral Therapies ◽  
Drug Concentrations ◽  
Specific Manner ◽  
Emerging Viral Diseases ◽  
Global Population

Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achievedin vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.

scholarly journals Protein Tyrosine and Serine/Threonine Phosphorylation in Oral Bacterial Dysbiosis and Bacteria-Host Interaction

2022 ◽  
Vol 11 ◽  
Author(s):  
Liang Ren ◽  
Daonan Shen ◽  
Chengcheng Liu ◽  
Yi Ding
Keyword(s):  
Community Development ◽  
Oral Bacteria ◽  
Bacterial Metabolism ◽  
Oral Microbiota ◽  
Bacterial Protein ◽  
Oral Diseases ◽  
Host Interactions ◽  
Host Interaction ◽  
Systemic Health

The human oral cavity harbors approximately 1,000 microbial species, and dysbiosis of the microflora and imbalanced microbiota-host interactions drive many oral diseases, such as dental caries and periodontal disease. Oral microbiota homeostasis is critical for systemic health. Over the last two decades, bacterial protein phosphorylation systems have been extensively studied, providing mounting evidence of the pivotal role of tyrosine and serine/threonine phosphorylation in oral bacterial dysbiosis and bacteria-host interactions. Ongoing investigations aim to discover novel kinases and phosphatases and to understand the mechanism by which these phosphorylation events regulate the pathogenicity of oral bacteria. Here, we summarize the structures of bacterial tyrosine and serine/threonine kinases and phosphatases and discuss the roles of tyrosine and serine/threonine phosphorylation systems in Porphyromonas gingivalis and Streptococcus mutans, emphasizing their involvement in bacterial metabolism and virulence, community development, and bacteria-host interactions.

scholarly journals Dynamic proteomics of HSV1 infection reveals molecular events that govern non-stochastic infection outcomes

2016 ◽  
Author(s):  
Nir Drayman ◽  
Omer Karin ◽  
Avi Mayo ◽  
Tamar Danon ◽  
Lev Shapira ◽  
...  
Keyword(s):  
Single Cells ◽  
Infection Process ◽  
Human Pathogen ◽  
Herpes Simplex Virus 1 ◽  
Host Interactions ◽  
Protein Levels ◽  
Molecular Events ◽  
Proteomics Approach ◽  
Infected Cells ◽  
Simplex Virus

AbstractViral infection is usually studied at the level of cell populations, averaging over hundreds of thousands of individual cells. Moreover, measurements are typically done by analyzing a few time points along the infection process. While informative, such measurements are limited in addressing how cell variability affects infection outcome. Here we employ dynamic proteomics to study virus-host interactions, using the human pathogen Herpes Simplex virus 1 as a model. We tracked >50,000 individual cells as they respond to HSV1 infection, allowing us to model infection kinetics and link infection outcome (productive or not) with the cell state at the time of initial infection. We find that single cells differ in their preexisting susceptibility to HSV1, and that this is partially mediated by their cell-cycle position. We also identify specific changes in protein levels and localization in infected cells, attesting to the power of the dynamic proteomics approach for studying virus-host interactions.

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