Pub Date : 2022-10-01DOI: 10.1016/j.coviro.2022.101273
Michael P Schwoerer, Alexander Ploss
Hepatitis C virus (HCV) is unable to infect mice, a fact that has severely limited their use as small-animal models for HCV pathogenesis and as tools for HCV vaccine development. HCV is blocked at various stages of its life cycle in mouse cells, due to incompatibility with host factors, the presence of dominant restriction factors, and effective immune responses. Molecular mechanisms for several such blocks have been characterized. The stepwise understanding of these limitations in mice will enable the development of an immunocompetent mouse that can fully support HCV infection and exhibit disease similar to that of infected humans.
{"title":"Barriers to hepatitis C virus infection in mice","authors":"Michael P Schwoerer, Alexander Ploss","doi":"10.1016/j.coviro.2022.101273","DOIUrl":"10.1016/j.coviro.2022.101273","url":null,"abstract":"<div><p>Hepatitis C virus (HCV) is unable to infect mice, a fact that has severely limited their use as small-animal models for HCV pathogenesis and as tools for HCV vaccine development. HCV is blocked at various stages of its life cycle in mouse cells, due to incompatibility with host factors, the presence of dominant restriction factors, and effective immune responses. Molecular mechanisms for several such blocks have been characterized. The stepwise understanding of these limitations in mice will enable the development of an immunocompetent mouse that can fully support HCV infection and exhibit disease similar to that of infected humans.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"56 ","pages":"Article 101273"},"PeriodicalIF":5.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/j.coviro.2022.101260
Samantha S Soldan, Troy E Messick, Paul M Lieberman
Epstein–Barr virus (EBV) establishes a lifelong latent infection that can be a causal agent for a diverse spectrum of cancers and autoimmune disease. A complex and dynamic viral lifecycle evades eradication by the host immune system and confounds antiviral therapeutic strategies. To date, there are no clinically approved vaccines or therapies that selectively target EBV as the underlying cause of EBV-associated disease. Here, we review the challenges and recent advances in the development of EBV-specific therapeutics for treatment of EBV-associated cancers.
{"title":"Therapeutic approaches to Epstein–Barr virus cancers","authors":"Samantha S Soldan, Troy E Messick, Paul M Lieberman","doi":"10.1016/j.coviro.2022.101260","DOIUrl":"10.1016/j.coviro.2022.101260","url":null,"abstract":"<div><p>Epstein–Barr virus (EBV) establishes a lifelong latent infection that can be a causal agent for a diverse spectrum of cancers and autoimmune disease. A complex and dynamic viral lifecycle evades eradication by the host immune system and confounds antiviral therapeutic<span> strategies. To date, there are no clinically approved vaccines or therapies that selectively target EBV as the underlying cause of EBV-associated disease. Here, we review the challenges and recent advances in the development of EBV-specific therapeutics for treatment of EBV-associated cancers.</span></p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"56 ","pages":"Article 101260"},"PeriodicalIF":5.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40381992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01DOI: 10.1016/j.coviro.2022.101270
Neil Kuehnle, Eva Gottwein
Kaposi’s sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). Here, we review what is known about human gene essentiality in PEL-derived cell lines. We provide an updated list of PEL-specific human gene dependencies, based on the improved definition of core essential genes across human cancer types. The requirements of PEL cell lines for interferon regulatory factor 4 (IRF4), basic leukine zipper ATF-like transcription factor (BATF), G1/S cyclin D2 (CCND2), CASP8 and FADD like apoptosis regulator (CFLAR), MCL1 apoptosis regulator (MCL1), and murine double minute 2 (MDM2) have been confirmed experimentally. KSHV co-opts IRF4 and BATF to drive superenhancer (SE)-mediated expression of IRF4 itself, MYC, and CCND2. IRF4 dependency of SE-mediated gene expression is shared with Epstein–Barr virus-transformed lymphoblastoid cell lines (LCLs) and human T-cell leukemia virus type 1-transformed adult T-cell leukemia/lymphoma (ATLL) cell lines, as well as several B-cell lymphomas of nonviral etiology. LCLs and ATLL cell lines similarly share dependencies on CCND2 and CFLAR with PEL, but also have distinct gene dependencies. Genetic dependencies could be exploited for therapeutic intervention in PEL and other cancers.
{"title":"Druggable host gene dependencies in primary effusion lymphoma","authors":"Neil Kuehnle, Eva Gottwein","doi":"10.1016/j.coviro.2022.101270","DOIUrl":"10.1016/j.coviro.2022.101270","url":null,"abstract":"<div><p>Kaposi’s sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). Here, we review what is known about human gene essentiality in PEL-derived cell lines. We provide an updated list of PEL-specific human gene dependencies, based on the improved definition of core essential genes across human cancer types. The requirements of PEL cell lines for interferon regulatory factor 4 (<em>IRF4</em>), basic leukine zipper ATF-like transcription factor (<em>BATF</em>), G1/S cyclin D2 (<em>CCND2</em>), CASP8 and FADD like apoptosis regulator <em>(CFLAR)</em>, MCL1 apoptosis regulator (<em>MCL1)</em>, and murine double minute 2 (<em>MDM2</em>) have been confirmed experimentally. KSHV co-opts IRF4 and BATF to drive superenhancer (SE)-mediated expression of <em>IRF4</em> itself, <em>MYC</em>, and <em>CCND2</em>. IRF4 dependency of SE-mediated gene expression is shared with Epstein–Barr virus-transformed lymphoblastoid cell lines (LCLs) and human T-cell leukemia virus type 1-transformed adult T-cell leukemia/lymphoma (ATLL) cell lines, as well as several B-cell lymphomas of nonviral etiology. LCLs and ATLL cell lines similarly share dependencies on <em>CCND2</em> and <em>CFLAR</em> with PEL, but also have distinct gene dependencies. Genetic dependencies could be exploited for therapeutic intervention in PEL and other cancers.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"56 ","pages":"Article 101270"},"PeriodicalIF":5.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.coviro.2022.101233
Elizabeth A Kennedy , Lori R Holtz
The human body is colonized by a multitude of bacteria, fungi, and viruses, which play important roles in health and disease. Microbial colonization during early life is thought to be a particularly important period with lasting consequences for health. Viral populations in the gut are particularly dynamic in early life before they stabilize in adulthood. The composition of the early-life virome is increasingly recognized as a determinant of disease later in life. Here, we review the development of the virome in healthy infants, as well as the role of the early-life virome in the development of disease states including diarrhea, malnutrition, and autoimmune diseases.
{"title":"Gut virome in early life: origins and implications","authors":"Elizabeth A Kennedy , Lori R Holtz","doi":"10.1016/j.coviro.2022.101233","DOIUrl":"10.1016/j.coviro.2022.101233","url":null,"abstract":"<div><p><span>The human body is colonized by a multitude of bacteria, fungi, and viruses, which play important roles in health and disease. </span>Microbial colonization during early life is thought to be a particularly important period with lasting consequences for health. Viral populations in the gut are particularly dynamic in early life before they stabilize in adulthood. The composition of the early-life virome is increasingly recognized as a determinant of disease later in life. Here, we review the development of the virome in healthy infants, as well as the role of the early-life virome in the development of disease states including diarrhea, malnutrition, and autoimmune diseases.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"55 ","pages":"Article 101233"},"PeriodicalIF":5.9,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47732945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.coviro.2022.101255
Venigalla B Rao, Jingen Zhu
The ability to deliver therapeutic genes and biomolecules into a human cell and restore a defective function has been the holy grail of medicine. Adeno-associated viruses and lentiviruses have been extensively used as delivery vehicles, but their capacity is limited to one (or two) gene(s). Bacteriophages are emerging as novel vehicles for gene therapy. The large 120 × 86-nm T4 capsid allows engineering of both its surface and its interior to incorporate combinations of DNAs, RNAs, proteins, and their complexes. In vitro assembly using purified components allows customization for various applications and for individualized therapies. Its large capacity, cell-targeting capability, safety, and inexpensive manufacturing could open unprecedented new possibilities for gene, cancer, and stem cell therapies. However, efficient entry into primary human cells and intracellular trafficking are significant barriers that must be overcome by gene engineering and evolution in order to translate phage-delivery technology from bench to bedside.
{"title":"Bacteriophage T4 as a nanovehicle for delivery of genes and therapeutics into human cells","authors":"Venigalla B Rao, Jingen Zhu","doi":"10.1016/j.coviro.2022.101255","DOIUrl":"10.1016/j.coviro.2022.101255","url":null,"abstract":"<div><p><span>The ability to deliver therapeutic genes and biomolecules into a human cell and restore a defective function has been the holy grail of medicine. Adeno-associated viruses and lentiviruses<span> have been extensively used as delivery vehicles, but their capacity is limited to one (or two) gene(s). Bacteriophages are emerging as novel vehicles for gene therapy. The large 120 × 86-nm T4 capsid allows engineering of both its surface and its interior to incorporate combinations of DNAs, RNAs, proteins, and their complexes. </span></span><em>In vitro</em><span> assembly using purified components allows customization for various applications and for individualized therapies. Its large capacity, cell-targeting capability, safety, and inexpensive manufacturing could open unprecedented new possibilities for gene, cancer, and stem cell therapies. However, efficient entry into primary human cells and intracellular trafficking are significant barriers that must be overcome by gene engineering and evolution in order to translate phage-delivery technology from bench to bedside.</span></p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"55 ","pages":"Article 101255"},"PeriodicalIF":5.9,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.coviro.2022.101254
Matthew Esparza, Prasanna Bhat, Beatriz MA Fontoura
As influenza-A viruses (IAV) replicate in the host cell nucleus, intranuclear pathways are usurped for viral gene expression. The eight genomic viral ribonucleoproteins (vRNPs) segments of IAV are transcribed and two generate viral mRNAs (M and NS) that undergo alternative splicing followed by export from the nucleus. The focus of this review is on viral RNA splicing and nuclear export. Recent mechanistic advances on M and NS splicing show differential regulation by RNA-binding proteins as well as distinct intranuclear localization. After a review of IAV splicing, we will discuss the nuclear export of viral mRNAs, which occur by interacting with specific constituents of the host mRNA export machinery that translocate viral mRNAs through the nuclear pore complex for translation in the cytoplasm.
{"title":"Viral–host interactions during splicing and nuclear export of influenza virus mRNAs","authors":"Matthew Esparza, Prasanna Bhat, Beatriz MA Fontoura","doi":"10.1016/j.coviro.2022.101254","DOIUrl":"10.1016/j.coviro.2022.101254","url":null,"abstract":"<div><p>As influenza-A viruses (IAV) replicate in the host cell nucleus<span>, intranuclear pathways are usurped for viral gene expression. The eight genomic viral ribonucleoproteins<span><span> (vRNPs) segments of IAV are transcribed and two generate viral mRNAs (M and NS) that undergo alternative splicing<span> followed by export from the nucleus. The focus of this review is on viral RNA splicing and nuclear export. Recent mechanistic advances on M and NS splicing show differential regulation by RNA-binding proteins as well as distinct intranuclear localization. After a review of IAV splicing, we will discuss the nuclear export of viral mRNAs, which occur by interacting with specific constituents of the host mRNA export machinery that translocate viral mRNAs through the </span></span>nuclear pore complex for translation in the cytoplasm.</span></span></p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"55 ","pages":"Article 101254"},"PeriodicalIF":5.9,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10751016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.coviro.2022.101248
Louis J Taylor , Emma L Keeler , Frederic D Bushman , Ronald G Collman
Anelloviridae and Redondoviridae are virus families with small, circular, single-stranded DNA genomes that are common components of the human virome. Despite their small genome size of less than 5000 bases, they are remarkably successful — anelloviruses colonize over 90% of adult humans, while the recently discovered redondoviruses have been found at up to 80% prevalence in some populations. Anelloviruses are present in blood and many organs, while redondoviruses are found mainly in the ororespiratory tract. Despite their high prevalence, little is known about their biology or pathogenic potential. In this review, we discuss anelloviruses and redondoviruses and explore their enigmatic roles in human health and disease.
{"title":"The enigmatic roles of Anelloviridae and Redondoviridae in humans","authors":"Louis J Taylor , Emma L Keeler , Frederic D Bushman , Ronald G Collman","doi":"10.1016/j.coviro.2022.101248","DOIUrl":"10.1016/j.coviro.2022.101248","url":null,"abstract":"<div><p><span><em>Anelloviridae</em></span> and <em>Redondoviridae</em><span><span><span><span> are virus families with small, circular, single-stranded DNA genomes that are common components of the </span>human virome. Despite their small </span>genome size of less than 5000 bases, they are remarkably successful — anelloviruses colonize over 90% of adult humans, while the recently discovered redondoviruses have been found at up to 80% prevalence in some populations. Anelloviruses are present in blood and many organs, while redondoviruses are found mainly in the ororespiratory tract. Despite their high prevalence, little is known about their biology or pathogenic potential. In this review, we discuss anelloviruses and redondoviruses and explore their enigmatic roles in </span>human health and disease.</span></p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"55 ","pages":"Article 101248"},"PeriodicalIF":5.9,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40531052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-01DOI: 10.1016/j.coviro.2022.101257
Christy S Varghese, Joanna L Parish, Jack Ferguson
Persistent virus infections are achieved when the intricate balance of virus replication, host-cell division and successful immune evasion is met. The genomes of persistent DNA viruses are either maintained as extrachromosomal episomes or can integrate into the host genome. Common to both these strategies of persistence is the chromatinisation of viral DNA by cellular histones which, like host DNA, are subject to epigenetic modification. Epigenetic repression of viral genes required for lytic replication occurs, while genes required for latent or persistent infection are maintained in an active chromatin state. Viruses utilise host-cell chromatin insulators, which function to maintain epigenetic boundaries and enforce this strict transcriptional programme. Here, we review insulator protein function in virus transcription control, focussing on CCCTC-binding factor (CTCF) and cofactors. We describe CTCF-dependent activities in virus transcription regulation through epigenetic and promoter–enhancer insulation, three-dimensional chromatin looping and manipulation of transcript splicing.
{"title":"Lying low-chromatin insulation in persistent DNA virus infection","authors":"Christy S Varghese, Joanna L Parish, Jack Ferguson","doi":"10.1016/j.coviro.2022.101257","DOIUrl":"10.1016/j.coviro.2022.101257","url":null,"abstract":"<div><p>Persistent virus infections are achieved when the intricate balance of virus replication, host-cell division and successful immune evasion is met. The genomes of persistent DNA viruses are either maintained as extrachromosomal episomes or can integrate into the host genome. Common to both these strategies of persistence is the chromatinisation of viral DNA by cellular histones which, like host DNA, are subject to epigenetic modification. Epigenetic repression of viral genes required for lytic replication occurs, while genes required for latent or persistent infection are maintained in an active chromatin state. Viruses utilise host-cell chromatin insulators, which function to maintain epigenetic boundaries and enforce this strict transcriptional programme. Here, we review insulator protein function in virus transcription control, focussing on CCCTC-binding factor (CTCF) and cofactors. We describe CTCF-dependent activities in virus transcription regulation through epigenetic and promoter–enhancer insulation, three-dimensional chromatin looping and manipulation of transcript splicing.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"55 ","pages":"Article 101257"},"PeriodicalIF":5.9,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1879625722000682/pdfft?md5=a934e4d351404403585abe735143b053&pid=1-s2.0-S1879625722000682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9158256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}