Productive (lytic) replication of DNA viruses elicits host cell DNA damage responses, which cause both beneficial and detrimental effects on viral replication. Viruses utilize them and selectively cancel the 'noisy' downstream signaling pathways, leading to maintain high S-phase CDK activities required for viral replication. To achieve this fine tuning of cellular environment, herpesviruses encode many (>70) genes in their genome, which are expressed in a strictly regulated temporal cascade (immediate-early, early, and late). Here, I introduce and discuss how Epstein-Barr virus, an oncogenic herpesvirus, hijacks the cellular environment and adapt it for the progeny production.
{"title":"[Molecular mechanisms of highly pathogenic viruses' replication and their applications for a novel drug discovery].","authors":"Shuzo Urata","doi":"10.2222/jsv.70.69","DOIUrl":"https://doi.org/10.2222/jsv.70.69","url":null,"abstract":"<p><p>Productive (lytic) replication of DNA viruses elicits host cell DNA damage responses, which cause both beneficial and detrimental effects on viral replication. Viruses utilize them and selectively cancel the 'noisy' downstream signaling pathways, leading to maintain high S-phase CDK activities required for viral replication. To achieve this fine tuning of cellular environment, herpesviruses encode many (>70) genes in their genome, which are expressed in a strictly regulated temporal cascade (immediate-early, early, and late). Here, I introduce and discuss how Epstein-Barr virus, an oncogenic herpesvirus, hijacks the cellular environment and adapt it for the progeny production.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"70 1","pages":"69-82"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38883718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Negative-strand RNA viruses do not possess a rigid viral shell, and their structures are flexible and fragile. We have applied various electron microscopies to analyze the morphologies of influenza and Ebola virus. Our studies have revealed the native interior and exterior ultrastructures of influenza virus as well as the assembly of Ebola virus core in atomic detail.
{"title":"[Structural studies on negative-strand RNA virus].","authors":"Yukihiko Sugita","doi":"10.2222/jsv.70.91","DOIUrl":"https://doi.org/10.2222/jsv.70.91","url":null,"abstract":"<p><p>Negative-strand RNA viruses do not possess a rigid viral shell, and their structures are flexible and fragile. We have applied various electron microscopies to analyze the morphologies of influenza and Ebola virus. Our studies have revealed the native interior and exterior ultrastructures of influenza virus as well as the assembly of Ebola virus core in atomic detail.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"70 1","pages":"91-100"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38883721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noroviruses commonly cause infectious gastroenteritis and massive food poisoning. There is an urgent need to elucidate the infection mechanism of noroviruses and to develop vaccines and therapeutic drugs. In addition to human disease, noroviruses have been implicated in animal disease. Noroviruses that cause murine diseases can be propagated in strained cultured cells, and for many years, murine norovirus has been used as a model for human noroviruses that could not be propagated in cultured cells. That model and advances in technology have been instrumental in basic studies of noroviruses. From structural biology, noroviruses undergo dynamic shape changes to improve their infectivity when they infect cells. New culture techniques have made human intestinal organoids available for studying the mechanisms of pathogenic expression of human noroviruses in the intestinal tract, mechanisms of infection growth, and the search for receptor molecules. Vaccines and antivirals using human intestinal organoids are under active development, and some are already in clinical trials. In this paper, I review the latest research results, vaccine development, and other advances from the history of norovirus discovery.
{"title":"[Review Norovirus].","authors":"Kazuhiko Katayama","doi":"10.2222/jsv.70.117","DOIUrl":"https://doi.org/10.2222/jsv.70.117","url":null,"abstract":"<p><p>Noroviruses commonly cause infectious gastroenteritis and massive food poisoning. There is an urgent need to elucidate the infection mechanism of noroviruses and to develop vaccines and therapeutic drugs. In addition to human disease, noroviruses have been implicated in animal disease. Noroviruses that cause murine diseases can be propagated in strained cultured cells, and for many years, murine norovirus has been used as a model for human noroviruses that could not be propagated in cultured cells. That model and advances in technology have been instrumental in basic studies of noroviruses. From structural biology, noroviruses undergo dynamic shape changes to improve their infectivity when they infect cells. New culture techniques have made human intestinal organoids available for studying the mechanisms of pathogenic expression of human noroviruses in the intestinal tract, mechanisms of infection growth, and the search for receptor molecules. Vaccines and antivirals using human intestinal organoids are under active development, and some are already in clinical trials. In this paper, I review the latest research results, vaccine development, and other advances from the history of norovirus discovery.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"70 2","pages":"117-128"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39433988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
At the end of December 2019, novel pneumonia emerged in Wuhan city, China, and it caused by novel coronavirus. Causative virus designated as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), and the diseases name was Coronavirus Disease 2019 (COVID-19). At first, SARS-CoV-2 was regarded as kind of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV). However, it was misunderstanding and SARS-CoV-2 was similar to human coronaviruses. Here, to help better understanding for SARS-CoV-2, the basis of coronavirus infection was described.
{"title":"[Basis of coronavirus infection, and SARS-CoV-2].","authors":"Kazuya Shirato","doi":"10.2222/jsv.70.155","DOIUrl":"https://doi.org/10.2222/jsv.70.155","url":null,"abstract":"At the end of December 2019, novel pneumonia emerged in Wuhan city, China, and it caused by novel coronavirus. Causative virus designated as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), and the diseases name was Coronavirus Disease 2019 (COVID-19). At first, SARS-CoV-2 was regarded as kind of SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV). However, it was misunderstanding and SARS-CoV-2 was similar to human coronaviruses. Here, to help better understanding for SARS-CoV-2, the basis of coronavirus infection was described.","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"70 2","pages":"155-166"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39433994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HTLV-1 inserts its viral genome into the host cellular DNA in the form of a provirus. The proviral DNA is a key to understand the persistence and pathogenesis of HTLV-1 infection. There has been a significant progress in proviral research due to technological advances on DNA sequencing.Next generation sequencing technology revolutionized our understanding of the human genome,showing how it is organized and regulated, not only by the nucleotide sequence itself but also by epigenetic features and higher-order chromatin structure. We will review recent findings regarding the role of HTLV-1 provirus in HTLV-1 infection.
{"title":"[The role of HTLV-1 provirus in clonal selection of the infected cells].","authors":"Misaki Matsuo, Paola Miyazato, Yorifumi Satou","doi":"10.2222/jsv.69.23","DOIUrl":"https://doi.org/10.2222/jsv.69.23","url":null,"abstract":"<p><p>HTLV-1 inserts its viral genome into the host cellular DNA in the form of a provirus. The proviral DNA is a key to understand the persistence and pathogenesis of HTLV-1 infection. There has been a significant progress in proviral research due to technological advances on DNA sequencing.Next generation sequencing technology revolutionized our understanding of the human genome,showing how it is organized and regulated, not only by the nucleotide sequence itself but also by epigenetic features and higher-order chromatin structure. We will review recent findings regarding the role of HTLV-1 provirus in HTLV-1 infection.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"69 1","pages":"23-28"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38388236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tm-1 is a semi-dominant resistance gene of tomato against tomato mosaic virus (ToMV). I identified the Tm-1 gene product through biochemical purification of an inhibitor of in vitro ToMV RNA replication from a tomato cell extract. Tm-1 protein binds ToMV replication proteins and inhibits formation of ToMV replication complex. Replication proteins of resistance-breaking ToMV mutants did not bind Tm-1, suggesting that ToMV mutants break the resistance by escaping the inhibitory interaction. Through molecular evolutionary approach, I found that a small part of the Tm-1 gene is under positive selection, suggesting that this region underwent rapid amino acid changes against selective pressure by ToMV infection. Crystal structures of a fragment of the Tm-1 protein and a complex between the Tm-1 fragment and a ToMV helicase domain fragment of replication proteins revealed that Tm-1 and ToMV have coevolved by changing both sides of the interaction interface. ToMV-susceptible tomato cultivars have a Tm-1 allele, tm-1, whose product neither binds to ToMV replication proteins nor inhibits RNA replication. I found that tm-1 inhibits multiplication of tobacco green mild mosaic virus (TMGMV) and pepper mild mottle virus (PMMoV), which does not adapt to tomato. A TMGMV mutant that can escape the inhibition by tm-1 lost the ability to suppress RNA silencing. Therefore, the multifunctionality of replication proteins is an evolutionary constraint of tobamoviruses that restricts their host ranges.
{"title":"[Studies of a plant antiviral defense system that inhibits viral RNA replication].","authors":"Kazuhiro Ishibashi","doi":"10.2222/jsv.69.83","DOIUrl":"https://doi.org/10.2222/jsv.69.83","url":null,"abstract":"Tm-1 is a semi-dominant resistance gene of tomato against tomato mosaic virus (ToMV). I identified the Tm-1 gene product through biochemical purification of an inhibitor of in vitro ToMV RNA replication from a tomato cell extract. Tm-1 protein binds ToMV replication proteins and inhibits formation of ToMV replication complex. Replication proteins of resistance-breaking ToMV mutants did not bind Tm-1, suggesting that ToMV mutants break the resistance by escaping the inhibitory interaction. Through molecular evolutionary approach, I found that a small part of the Tm-1 gene is under positive selection, suggesting that this region underwent rapid amino acid changes against selective pressure by ToMV infection. Crystal structures of a fragment of the Tm-1 protein and a complex between the Tm-1 fragment and a ToMV helicase domain fragment of replication proteins revealed that Tm-1 and ToMV have coevolved by changing both sides of the interaction interface. ToMV-susceptible tomato cultivars have a Tm-1 allele, tm-1, whose product neither binds to ToMV replication proteins nor inhibits RNA replication. I found that tm-1 inhibits multiplication of tobacco green mild mosaic virus (TMGMV) and pepper mild mottle virus (PMMoV), which does not adapt to tomato. A TMGMV mutant that can escape the inhibition by tm-1 lost the ability to suppress RNA silencing. Therefore, the multifunctionality of replication proteins is an evolutionary constraint of tobamoviruses that restricts their host ranges.","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"69 1","pages":"83-90"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38388242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Because of the concerns about aseptic meningitis due to Japanese domestic mumps vaccine strains, the routine mumps immunization program has not yet been introduced in Japan, and it resulted in the situation where the major mumps epidemics occur every 4-5 years. However, the fact that at least 348 mumps hearing loss cases were reported during the recent epidemic period in 2015-2016, argues that the introduction of the routine mumps immunization program is an urgent issue for us. In contrast, 122 countries employ mumps-containing vaccines for nationwide immunization programs by 2018, of which 117 apply 2-dose vaccination regimens, and many of them use Jeryl-Lynn containing measles-mumps-rubella (MMR) vaccines. While in these countries, where mumps seemed to have been controlled, mumps resurgented in the 2000s. Although, the concerns surrounding mumps vaccination are extremely different in Japan and abroad, both of them link to the inherent characteristics of mumps vaccine, in which it is hard to balance the safety and the efficacy. In order to promptly introduce the routine mumps immunization program in Japan, Japanese domestic mumps vaccine strains need to be re-evaluated based on the latest evidence. Furthermore, from a long-range viewpoint, a novel mumps vaccine should be developed, which combines the safety and the efficacy.
{"title":"[Future perspectives of mumps vaccine].","authors":"Minoru Kidokoro","doi":"10.2222/jsv.68.125","DOIUrl":"https://doi.org/10.2222/jsv.68.125","url":null,"abstract":"<p><p>Because of the concerns about aseptic meningitis due to Japanese domestic mumps vaccine strains, the routine mumps immunization program has not yet been introduced in Japan, and it resulted in the situation where the major mumps epidemics occur every 4-5 years. However, the fact that at least 348 mumps hearing loss cases were reported during the recent epidemic period in 2015-2016, argues that the introduction of the routine mumps immunization program is an urgent issue for us. In contrast, 122 countries employ mumps-containing vaccines for nationwide immunization programs by 2018, of which 117 apply 2-dose vaccination regimens, and many of them use Jeryl-Lynn containing measles-mumps-rubella (MMR) vaccines. While in these countries, where mumps seemed to have been controlled, mumps resurgented in the 2000s. Although, the concerns surrounding mumps vaccination are extremely different in Japan and abroad, both of them link to the inherent characteristics of mumps vaccine, in which it is hard to balance the safety and the efficacy. In order to promptly introduce the routine mumps immunization program in Japan, Japanese domestic mumps vaccine strains need to be re-evaluated based on the latest evidence. Furthermore, from a long-range viewpoint, a novel mumps vaccine should be developed, which combines the safety and the efficacy.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"68 2","pages":"125-136"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38387415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Challenges toward elimination of rubella in Japan].","authors":"Yoshio Mori","doi":"10.2222/jsv.68.157","DOIUrl":"https://doi.org/10.2222/jsv.68.157","url":null,"abstract":"","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"68 2","pages":"157-160"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38387828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In autumn 2015, the detection number of enterovirus D68 increased in Japan, and many cases of severe bronchial asthma and acute flaccid paralysis were observed. At that time, among WPR countries Japan was a country not implementing AFP surveillance, which was implemented in 174 countries in 194 WHO member countries. Since May 2018, ''acute flaccid paralysis (excluding poliomyelitis)'' was introduced into the notification diseases based on the Infectious Disease Law. Acute flaccid paralysis cases under 15 years old were reported to the National Epidemiological Surveillance of Infectious Diseases (NESID) system within 7 days after the diagnosis. From around October 2018, the number of AFP reports has increased. Many cases were preschool children, and the median age was 4 years old.
{"title":"[Epidemiology of enterovirus D68 infection].","authors":"Keiko Tanaka-Taya","doi":"10.2222/jsv.68.161","DOIUrl":"https://doi.org/10.2222/jsv.68.161","url":null,"abstract":"<p><p>In autumn 2015, the detection number of enterovirus D68 increased in Japan, and many cases of severe bronchial asthma and acute flaccid paralysis were observed. At that time, among WPR countries Japan was a country not implementing AFP surveillance, which was implemented in 174 countries in 194 WHO member countries. Since May 2018, ''acute flaccid paralysis (excluding poliomyelitis)'' was introduced into the notification diseases based on the Infectious Disease Law. Acute flaccid paralysis cases under 15 years old were reported to the National Epidemiological Surveillance of Infectious Diseases (NESID) system within 7 days after the diagnosis. From around October 2018, the number of AFP reports has increased. Many cases were preschool children, and the median age was 4 years old.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"68 2","pages":"161-164"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38387829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human T-cell leukemia virus type 1 (HTLV-1) is the world's first retrovirus with pathogenicity to cause adult T-cell leukemia-lymphoma (ATL) and chronic inflammatory diseases,such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis. As the virological characteristic, HTLV-1 can transmit efficiently only through cell-to-cell contact. Spread of infection and viral persistence is ingeniously driven by several viral genes as exemplified by HTLV-1 bZIP factor (HBZ) and tax. After the infection, the virus promotes proliferation and immortalization of the infected cells with acculturating immunophenotype into effector/memory T cells. In addition, HBZ enhances expression of co-inhibitory receptors on the surface of infected cells, potentially leading to suppression of host immune responses. These viral strategies can also result in unforeseen by-product, the pathogenicity of HTLV-1-associated diseases. In this review, with recent progress of HTLV-1 researches, we focus on astute regulation systems of the viral genes developed by HTLV-1.
{"title":"[Astute strategies of HTLV-1 with driven viral genes].","authors":"Kosuke Toyoda, Jun-Ichirou Yasunaga, Masao Matsuoka","doi":"10.2222/jsv.69.37","DOIUrl":"https://doi.org/10.2222/jsv.69.37","url":null,"abstract":"<p><p>Human T-cell leukemia virus type 1 (HTLV-1) is the world's first retrovirus with pathogenicity to cause adult T-cell leukemia-lymphoma (ATL) and chronic inflammatory diseases,such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis. As the virological characteristic, HTLV-1 can transmit efficiently only through cell-to-cell contact. Spread of infection and viral persistence is ingeniously driven by several viral genes as exemplified by HTLV-1 bZIP factor (HBZ) and tax. After the infection, the virus promotes proliferation and immortalization of the infected cells with acculturating immunophenotype into effector/memory T cells. In addition, HBZ enhances expression of co-inhibitory receptors on the surface of infected cells, potentially leading to suppression of host immune responses. These viral strategies can also result in unforeseen by-product, the pathogenicity of HTLV-1-associated diseases. In this review, with recent progress of HTLV-1 researches, we focus on astute regulation systems of the viral genes developed by HTLV-1.</p>","PeriodicalId":75275,"journal":{"name":"Uirusu","volume":"69 1","pages":"37-46"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38388238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}