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MBio Apr 2023Viruses lack the properties to replicate independently due to the limited resources encoded in their genome; therefore, they hijack the host cell machinery to replicate... (Review)
Review
Viruses lack the properties to replicate independently due to the limited resources encoded in their genome; therefore, they hijack the host cell machinery to replicate and survive. Picornaviruses get the prerequisite for effective protein synthesis through specific sequences known as internal ribosome entry sites (IRESs). In the past 2 decades, significant progress has been made in identifying different types of IRESs in picornaviruses. This review will discuss the past and current findings related to the five different types of IRESs and various internal ribosome entry site -acting factors (ITAFs) that either promote or suppress picornavirus translation and replication. Some IRESs are inefficient and thus require ITAFs. To achieve their full efficiency, they recruit various ITAFs, which enable them to translate more effectively and efficiently, except type IV IRES, which does not require any ITAFs. Although there are two kinds of ITAFs, one promotes viral IRES-dependent translation, and the second type restricts. Picornaviruses IRESs are classified into five types based on their use of sequence, ITAFs, and initiation factors. Some ITAFs regulate IRES activity by localizing to the viral replication factories in the cytoplasm. Also, some drugs, chemicals, and herbal extracts also regulate viral IRES-dependent translation and replication. Altogether, this review will elaborate on our understanding of the past and recent advancements in the IRES-dependent translation and replication of picornaviruses. The family is divided into 68 genera and 158 species. The viruses belonging to this family range from public health importance, such as poliovirus, enterovirus A71, and hepatitis A virus, to animal viruses of great economic importance, such as foot-and-mouth disease virus. The genomes of picornaviruses contain 5' untranslated regions (5' UTRs), which possess crucial and highly structured stem-loops known as IRESs. IRES assemble the ribosomes and facilitate the cap-independent translation. Virus-host interaction is a hot spot for researchers, which warrants deep insight into understanding viral pathogenesis better and discovering new tools and ways for viral restriction to improve human and animal health. The cap-independent translation in the majority of picornaviruses is modulated by ITAFs, which bind to various IRES regions to initiate the translation. The discoveries of ITAFs substantially contributed to understanding viral replication behavior and enhanced our knowledge about virus-host interaction more effectively than ever before. This review discussed the various types of IRESs found in , past and present discoveries regarding ITAFs, and their mechanism of action. The herbal extracts, drugs, and chemicals, which indicated their importance in controlling viruses, were also summarized. In addition, we discussed the movement of ITAFs from the nucleus to viral replication factories. We believe this review will stimulate researchers to search for more novel ITAFs, drugs, herbal extracts, and chemicals, enhancing the understanding of virus-host interaction.
Topics: Animals; Humans; Picornaviridae; Internal Ribosome Entry Sites; Foot-and-Mouth Disease Virus; Ribosomes; Hepatitis A virus; Protein Biosynthesis; RNA, Viral
PubMed: 36939331
DOI: 10.1128/mbio.00358-23 -
European Journal of Pediatrics Aug 2016Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in... (Review)
Review
UNLABELLED
Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of enterovirus and parechovirus infection in children.
CONCLUSIONS
EV and HPeV infections are a frequent cause of infection in childhood. The clinical presentation is diverse. RT-qPCR is the best way to detect an EV or HPeV. Cerebrospinal fluid, blood and feces have the highest sensitivity for detecting an EV or HPeV. There is no treatment for EV and HPeV infections. Two vaccines against EV 71 are just licensed in China and will be available on the private market. Little is known about the prognosis of EV and HPeV infections.
WHAT IS KNOWN
•EV and HPeV are a frequent cause of infection in children. What is new: •This review gives a brief overview over EV and HPeV infection in children.
Topics: Child; Enterovirus; Enterovirus Infections; Humans; Parechovirus; Picornaviridae Infections; Prevalence; Prognosis; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 27156106
DOI: 10.1007/s00431-016-2725-7 -
Microbiology and Molecular Biology... Sep 2014The Picornaviridae represent a large family of small plus-strand RNA viruses that cause a bewildering array of important human and animal diseases. Morphogenesis is the... (Review)
Review
The Picornaviridae represent a large family of small plus-strand RNA viruses that cause a bewildering array of important human and animal diseases. Morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and RNA replication. Although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this process. Most of the information available has been derived from studies of enteroviruses, in particular poliovirus, where recent evidence has shown that, surprisingly, the specificity of encapsidation is governed by a viral protein-protein interaction that does not involve an RNA packaging signal. In this review, we make an attempt to summarize what is currently known about the following topics: (i) encapsidation intermediates, (ii) the specificity of encapsidation (iii), viral and cellular factors that are required for encapsidation, (iv) inhibitors of encapsidation, and (v) a model of enterovirus encapsidation. Finally, we compare some features of picornavirus morphogenesis with those of other plus-strand RNA viruses.
Topics: Animals; Antiviral Agents; Capsid; Genome, Viral; Host-Pathogen Interactions; Humans; Morphogenesis; Picornaviridae; Picornaviridae Infections; RNA, Viral; Virus Assembly
PubMed: 25184560
DOI: 10.1128/MMBR.00012-14 -
Viruses Mar 2021Picornaviruses are comprised of a positive-sense RNA genome surrounded by a protein shell (or capsid). They are ubiquitous in vertebrates and cause a wide range of... (Review)
Review
Picornaviruses are comprised of a positive-sense RNA genome surrounded by a protein shell (or capsid). They are ubiquitous in vertebrates and cause a wide range of important human and animal diseases. The genome encodes a single large polyprotein that is processed to structural (capsid) and non-structural proteins. The non-structural proteins have key functions within the viral replication complex. Some, such as 3D (the RNA dependent RNA polymerase) have conserved functions and participate directly in replicating the viral genome, whereas others, such as 3A, have accessory roles. The 3A proteins are highly divergent across the and have specific roles both within and outside of the replication complex, which differ between the different genera. These roles include subverting host proteins to generate replication organelles and inhibition of cellular functions (such as protein secretion) to influence virus replication efficiency and the host response to infection. In addition, 3A proteins are associated with the determination of host range. However, recent observations have challenged some of the roles assigned to 3A and suggest that other viral proteins may carry them out. In this review, we revisit the roles of 3A in the picornavirus life cycle. The 3AB precursor and mature 3A have distinct functions during viral replication and, therefore, we have also included discussion of some of the roles assigned to 3AB.
Topics: Genome, Viral; Humans; Picornaviridae; Protein Transport; RNA, Viral; Viral Proteins; Virus Replication
PubMed: 33799649
DOI: 10.3390/v13030456 -
Microbiology Spectrum Jun 2016Infections with enteroviruses and human parechoviruses are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality.... (Review)
Review
Infections with enteroviruses and human parechoviruses are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. Individuals with B-cell-related immunodeficiencies are at risk for severe enteroviral infections, usually a chronic and fatal meningoencephalitis. In transplant recipients and patients with malignancy, enterovirus infections typically involve the respiratory tract, but cases of severe, disseminated infection have been described. The mainstay of diagnosis for enterovirus and human parechovirus infections involves the use of molecular diagnostic techniques. However, routine nucleic acid-detection methods for enteroviruses will not detect human parechoviruses. Laboratory diagnosis of these viral infections is important in determining a patient's prognosis and guiding clinical management.
Topics: B-Lymphocytes; Enterovirus; Enterovirus Infections; Humans; Immunocompromised Host; Molecular Diagnostic Techniques; Neoplasms; Parechovirus; Picornaviridae Infections; Transplant Recipients; Transplantation
PubMed: 27337462
DOI: 10.1128/microbiolspec.DMIH2-0006-2015 -
Current Opinion in Virology Dec 2021Structure-based antiviral developments in the past two years have been dominated by the structure determination and inhibition of SARS-CoV-2 proteins and new lead... (Review)
Review
Structure-based antiviral developments in the past two years have been dominated by the structure determination and inhibition of SARS-CoV-2 proteins and new lead molecules for picornaviruses. The SARS-CoV-2 spike protein has been targeted successfully with antibodies, nanobodies, and receptor protein mimics effectively blocking receptor binding or fusion. The two most promising non-structural proteins sharing strong structural and functional conservation across virus families are the main protease and the RNA-dependent RNA polymerase, for which design and reuse of broad range inhibitors already approved for use has been an attractive avenue. For picornaviruses, the increasing recognition of the transient expansion of the capsid as a critical transition towards RNA release has been targeted through a newly identified, apparently widely conserved, druggable, interprotomer pocket preventing viral entry. We summarize some of the key papers in these areas and ponder the practical uses and contributions of molecular modeling alongside empirical structure determination.
Topics: Animals; Antiviral Agents; Drug Delivery Systems; Drug Design; Drug Repositioning; Humans; Picornaviridae; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34564030
DOI: 10.1016/j.coviro.2021.09.005 -
Viruses Apr 2021Rhinoviruses (RVs) are the etiological agents of upper respiratory tract infections, particularly the common cold. Infections in the lower respiratory tract is shown to... (Review)
Review
Rhinoviruses (RVs) are the etiological agents of upper respiratory tract infections, particularly the common cold. Infections in the lower respiratory tract is shown to cause severe disease and exacerbations in asthma and COPD patients. Viruses being obligate parasites, hijack host cell pathways such as programmed cell death to suppress host antiviral responses and prolong viral replication and propagation. RVs are non-enveloped positive sense RNA viruses with a lifecycle fully contained within the cytoplasm. Despite decades of study, the details of how RVs exit the infected cell are still unclear. There are some diverse studies that suggest a possible role for programmed cell death. In this review, we aimed to consolidate current literature on the impact of RVs on cell death to inform future research on the topic. We searched peer reviewed English language literature in the past 21 years for studies on the interaction with and modulation of cell death pathways by RVs, placing it in the context of the broader knowledge of these interconnected pathways from other systems. Our review strongly suggests a role for necroptosis and/or autophagy in RV release, with the caveat that all the literature is based on RV-A and RV-B strains, with no studies to date examining the interaction of RV-C strains with cell death pathways.
Topics: Autophagy; Cell Death; Humans; Necroptosis; Picornaviridae Infections; Rhinovirus; Virus Replication
PubMed: 33916958
DOI: 10.3390/v13040629 -
FEBS Open Bio Jun 2022The genome of viruses classified as picornaviruses consists of a single monocistronic positive strand RNA. The coding capacity of these RNA viruses is rather limited,... (Review)
Review
The genome of viruses classified as picornaviruses consists of a single monocistronic positive strand RNA. The coding capacity of these RNA viruses is rather limited, and thus, they rely on the cellular machinery for their viral replication cycle. Upon the entry of the virus into susceptible cells, the viral RNA initially competes with cellular mRNAs for access to the protein synthesis machinery. Not surprisingly, picornaviruses have evolved specialized strategies that successfully allow the expression of viral gene products, which we outline in this review. The main feature of all picornavirus genomes is the presence of a heavily structured RNA element on the 5´UTR, referred to as an internal ribosome entry site (IRES) element, which directs viral protein synthesis as well and, consequently, triggers the subsequent steps required for viral replication. Here, we will summarize recent studies showing that picornavirus IRES elements consist of a modular structure, providing sites of interaction for ribosome subunits, eIFs, and a selective group of RNA-binding proteins.
Topics: Internal Ribosome Entry Sites; Picornaviridae; RNA, Messenger; RNA, Viral; Virus Replication
PubMed: 35313388
DOI: 10.1002/2211-5463.13400 -
Viruses Jan 2020The Special Issue "Human Picornaviruses" in "" (Submission Deadline 30 September 2019, https://www.mdpi.com/journal/viruses/special_issues/Picornaviruses) includes...
The Special Issue "Human Picornaviruses" in "" (Submission Deadline 30 September 2019, https://www.mdpi.com/journal/viruses/special_issues/Picornaviruses) includes twelve original articles and four reviews with a wide range of topics [...].
Topics: Humans; Picornaviridae; Picornaviridae Infections
PubMed: 31941146
DOI: 10.3390/v12010093 -
Viruses Jun 2021Picornaviruses are positive-stranded RNA viruses. Even though replication and translation of their genome take place in the cytoplasm, these viruses evolved different... (Review)
Review
Picornaviruses are positive-stranded RNA viruses. Even though replication and translation of their genome take place in the cytoplasm, these viruses evolved different strategies to disturb nucleocytoplasmic trafficking of host proteins and RNA. The major targets of picornavirus are the phenylalanine-glycine (FG)-nucleoporins, which form a mesh in the central channel of the nuclear pore complex through which protein cargos and karyopherins are actively transported in both directions. Interestingly, while enteroviruses use the proteolytic activity of their 2A protein to degrade FG-nucleoporins, cardioviruses act by triggering phosphorylation of these proteins by cellular kinases. By targeting the nuclear pore complex, picornaviruses recruit nuclear proteins to the cytoplasm, where they increase viral genome translation and replication; they affect nuclear translocation of cytoplasmic proteins such as transcription factors that induce innate immune responses and retain host mRNA in the nucleus thereby preventing cell emergency responses and likely making the ribosomal machinery available for translation of viral RNAs.
Topics: Active Transport, Cell Nucleus; Cell Nucleus; Humans; Karyopherins; Nuclear Pore; Nuclear Pore Complex Proteins; Picornaviridae; Picornaviridae Infections; Species Specificity; Viral Proteins; Virus Replication; ran GTP-Binding Protein
PubMed: 34201715
DOI: 10.3390/v13071210