scholarly journals Hijacking of Lipid Droplets by Hepatitis C, Dengue and Zika Viruses—From Viral Protein Moonlighting to Extracellular Release

2020 ◽  
Vol 21 (21) ◽  
pp. 7901 ◽  
Author(s):  
Alexandra P.M. Cloherty ◽  
Andrea D. Olmstead ◽  
Carla M.S. Ribeiro ◽  
François Jean
Keyword(s):  
Hepatitis C ◽  
Viral Infection ◽  
Host Cell ◽  
Lipid Droplets ◽  
Viral Proteins ◽  
Biological Properties ◽  
Protein Functions ◽  
Associated Proteins ◽  
Viral Lifecycle ◽  
Moonlighting Functions

Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. Flaviviridae members, including hepatitis C, dengue and Zika viruses, extensively manipulate host lipid metabolism, underlining the importance of lipid droplets (LDs) in viral infection. LDs are dynamic cytoplasmic organelles that can act as sequestration platforms for a unique subset of host and viral proteins. Transient recruitment and mobilization of proteins to LDs during viral infection impacts host-cell biological properties, LD functionality and canonical protein functions. Notably, recent studies identified LDs in the nucleus and also identified that LDs are transported extracellularly via an autophagy-mediated mechanism, indicating a novel role for autophagy in Flaviviridae infections. These developments underline an unsuspected diversity and localization of LDs and potential moonlighting functions of LD-associated proteins during infection. This review summarizes recent breakthroughs concerning the LD hijacking activities of hepatitis C, dengue and Zika viruses and potential roles of cytoplasmic, nuclear and extracellular LD-associated viral proteins during infection.

scholarly journals Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1597
Author(s):  
Olga V. Iarovaia ◽  
Elena S. Ioudinkova ◽  
Artem K. Velichko ◽  
Sergey V. Razin
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Viral Infection ◽  
Host Cell ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Infection Process ◽  
Regulatory Pathways ◽  
Nucleolar Proteins

Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection.

scholarly journals Role of transferrin receptor in hepatitis C viral infection

2018 ◽  
Vol 7 (2) ◽  
pp. 33-37
Author(s):  
Quan Liang
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Host Cell ◽  
Transferrin Receptor ◽  
Primary Liver Cancer ◽  
Viral Proteins ◽  
Cell Entry ◽  
Specific Receptor ◽  
Host Cell Membrane

Abstract Hepatitis C virus (HCV) is the main pathogen causing chronic hepatitis and primary liver cancer. Various viral proteins and host cell molecules are involved in the HCV cell entry, but the mechanism of infection has not been completely elucidated. The transferrin receptor can act as a receptor for many viruses during cell entry. The transferrin receptor is not only closely related to HCV-induced iron metabolism disorders but also mediates the fusion of HCV with the host cell membrane as a specific receptor for CD81-dependent viral adhesion.

Interplay between host cell and hepatitis C virus in regulating viral replication

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Johannes G. Bode ◽  
Erwin D. Brenndörfer ◽  
Juliane Karthe ◽  
Dieter Häussinger
Keyword(s):  
Life Cycle ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Host Cell ◽  
Growth Factor Receptor ◽  
Protein Translation ◽  
Viral Life Cycle ◽  
Cellular Growth ◽  
Viral Genomes ◽  
Associated Proteins

Abstract Viral life cycle as that of the hepatitis C virus (HCV) completely relies on host cell infrastructure, presupposing that the virus has evolved mechanisms to utilize and control all cellular molecules or pathways required for viral life cycle. Hence, HCV must have acquired the ability to gain access to key pathways controlling processes, such as cell growth, apoptosis and protein synthesis, which are all considered to also be crucial for liver regeneration. This occurs in a balanced way permitting persistent replication of viral genomes and production of infectious particles without endangering host cell viability and survival. In particular during the last decade, accumulating evidence indicates that HCV utilizes signaling pathways of the host with major impact on cellular growth, viability, cell cycle or cellular metabolism, such as epidermal growth factor-receptor mediated signals, the PI3K/Akt cascade or the family of Src kinases. Furthermore, HCV specifically interacts with parts of the cellular machinery involved in protein translation, processing, maturation and transport, such as components of the translation complex, the heat shock protein family, the immunophilins or the vesicle-associated membrane protein-associated proteins A and B. The present review focuses on the interplay between viral proteins and these factors of the host cell enabling the virus to utilize host cell infrastructure.

The diagnosis of hepatitis C viral infection

2014 ◽  
Vol 155 (26) ◽  
pp. 1019-1023
Author(s):  
Judit Gervain
Keyword(s):  
Hepatitis C ◽  
Nucleic Acid ◽  
Viral Infection ◽  
Structural Changes ◽  
Viral Infections ◽  
Transient Elastography ◽  
Viral Nucleic Acid ◽  
Length Of Treatment ◽  
Subtype B

The successful therapy of hepatitis C viral infection requires that the illness is diagnosed before the development of structural changes of the liver. Testing is stepwise consisting of screening, diagnosis, and anti-viral therapy follow-up. For these steps there are different biochemical, serological, histological and molecular biological methods available. For screening, alanine aminotransferase and anti-HCV tests are used. The diagnosis of infection is confirmed using real-time polymerase chain reaction of the viral nucleic acid. Before initiation of the therapy liver biopsy is recommended to determine the level of structural changes in the liver. Alternatively, transient elastography or blood biomarkers may be also used for this purpose. Differential diagnosis should exclude the co-existence of other viral infections and chronic hepatitis due to other origin, with special attention to the presence of autoantibodies. The outcome of the antiviral therapy and the length of treatment are mainly determined by the viral genotype. In Hungary, most patients are infected with genotype 1, subtype b. The polymorphism type that occurs in the single nucleotide located next to the interleukin 28B region in chromosome 19 and the viral polymorphism type Q80K for infection with HCV 1a serve as predictive therapeutic markers. The follow-up of therapy is based on the quantitative determination of viral nucleic acid according to national and international protocols and should use the same method and laboratory throughout the treatment of an individual patient. Orv. Hetil., 2014, 155(26), 1019–1023.

Possible Targets and Therapies of SARS-CoV-2 Infection

2020 ◽  
Vol 20 (18) ◽  
pp. 1900-1907
Author(s):  
Kasturi Sarkar ◽  
Parames C. Sil ◽  
Seyed Fazel Nabavi ◽  
Ioana Berindan-Neagoe ◽  
Cosmin Andrei Cismaru ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Viral Infection ◽  
Human Activity ◽  
Viral Proteins ◽  
Therapeutic Agents ◽  
Effective Control ◽  
Human Society ◽  
Global Spread ◽  
Repurposed Drugs

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.

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