Jack Chun-Chieh Hsu , Maudry Laurent-Rolle , Peter Cresswell
{"title":"Translational regulation of viral RNA in the type I interferon response","authors":"Jack Chun-Chieh Hsu , Maudry Laurent-Rolle , Peter Cresswell","doi":"10.1016/j.crviro.2021.100012","DOIUrl":"10.1016/j.crviro.2021.100012","url":null,"abstract":"<div><p>The innate immune response serves as a robust first line of defense against pathogens, protecting the host from infectious organisms in a rapid and antigen-independent manner. Viral infection activates the type I interferon (IFN-I) response, leading to the production of hundreds of interferon-stimulated genes (ISGs). Many of these ISG-encoded proteins restrict viral infection by a variety of mechanisms that inhibit different stages of the virus life cycle. Translation inhibition, which restricts the production of viral proteins and host factors required for viral replication, is a common cellular response to viral infection. The IFN-I response induces translation inhibition primarily through the expression of ISG-encoded proteins. These proteins employ a variety of mechanisms to inhibit either global or virus-specific translation, resulting in restriction of viral replication and dissemination. In this graphical review, we provide an overview of the critical role of ISG-encoded proteins in translational regulation during the IFN-I response and viral infection. We focus on the molecular mechanisms by which ISG-encoded proteins restrict viral translation, including blocking the assembly of the translation machinery and inducing RNA degradation.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"2 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666478X21000064/pdfft?md5=d314f0dadb770dcc8cf441ed441af23b&pid=1-s2.0-S2666478X21000064-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48154369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BRD4 downregulation inhibits the viability of cervical cancer cells without affecting viral oncoprotein expression","authors":"Veronica Canarte , Karl Munger","doi":"10.1016/j.crviro.2021.100010","DOIUrl":"10.1016/j.crviro.2021.100010","url":null,"abstract":"<div><p>Human papillomavirus (HPV) expressing cervical cancer lines are sensitized to inhibition of the Bromodomain Containing 4 (BRD4) epigenetic reader protein and this has been linked to decreased expression of the viral E6 and E7 oncoproteins from the viral promoter. Here we show that BRD4 depletion can inhibit the viability of HPV16-positive cervical carcinoma cells and HPV16 E6/E7 expressing cells through a mechanism that is independent of affecting viral oncoprotein expression.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"2 ","pages":"Article 100010"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crviro.2021.100010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54125775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elías Cuesta-Llavona , Guillermo M. Albaiceta , Marta García-Clemente , Israel D. Duarte-Herrera , Laura Amado-Rodríguez , Tamara Hermida-Valverde , Ana I. Enríquez-Rodriguez , Cristina Hernández-González , Santiago Melón , Marta E. Alvarez-Argüelles , José A. Boga , Susana Rojo-Alba , Daniel Vázquez-Coto , Juan Gómez , Eliecer Coto PhD
{"title":"Association between the interferon-induced transmembrane protein 3 gene (IFITM3) rs34481144 / rs12252 haplotypes and COVID-19","authors":"Elías Cuesta-Llavona , Guillermo M. Albaiceta , Marta García-Clemente , Israel D. Duarte-Herrera , Laura Amado-Rodríguez , Tamara Hermida-Valverde , Ana I. Enríquez-Rodriguez , Cristina Hernández-González , Santiago Melón , Marta E. Alvarez-Argüelles , José A. Boga , Susana Rojo-Alba , Daniel Vázquez-Coto , Juan Gómez , Eliecer Coto PhD","doi":"10.1016/j.crviro.2021.100016","DOIUrl":"https://doi.org/10.1016/j.crviro.2021.100016","url":null,"abstract":"<div><p>The interferon induced transmembrane-protein 3 (IFITM3) plays an important role in the defence against viral infection. <em>IFITM3</em> gene variants have been linked to differences in expression and associated with the risk of severe influenza by some authors. More recently, these variants have been associated with the risk of COVID-19 after SARS-CoV-2 infection. We determined the effect of two common <em>IFITM3</em> polymorphisms (rs34481144 C/T and rs12252 A/G) on the risk of hospitalization due to COVID-19 by comparing 484 patients (152 required support in thr intensive care unit, ICU) and 182 age and sex matched controls (no disease symptoms). We found significantly higher frequencies of rs34481144 T and rs12252 G carriers among the patients (OR = 2.02 and OR = 1.51, respectively). None of the two variants were associated with ICU-admission or death. We found a significantly higher frequency of rs34481144 CC + rs12252 AA genotype carriers among the controls, suggesting a protective effect (<strong>p</strong> = <strong>0.001, OR</strong> = <strong>0.56, 95%CI</strong> = <strong>0.40</strong>–<strong>0.80).</strong> Moreover, haplotype rs34481144 C - rs12252 A was significantly increased in the controls (p = 0.008, OR = 0.71, 95%CI = 0.55–0.91).</p><p>Our results showed a significant effect of the <em>IFITM3</em> variants in the risk for hospitalization after SARS-CoV-2 infection.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"2 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666478X21000106/pdfft?md5=39328f73561396e183881376e34456df&pid=1-s2.0-S2666478X21000106-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92114981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SARS-CoV-2 NSP1 C-terminal (residues 131–180) is an intrinsically disordered region in isolation","authors":"Amit Kumar , Ankur Kumar , Prateek Kumar , Neha Garg , Rajanish Giri","doi":"10.1016/j.crviro.2021.100007","DOIUrl":"10.1016/j.crviro.2021.100007","url":null,"abstract":"<div><p>The NSP1– C terminal structure in complex with ribosome using cryo-EM is available now, and the N-terminal region structure in isolation is also deciphered in literature. However, as a reductionist approach, the conformation of NSP1– C terminal region (NSP1-CTR; amino acids 131–180) has not been studied in isolation. We found that NSP1-CTR conformation is disordered in an aqueous solution. Further, we examined the conformational propensity towards alpha-helical structure using trifluoroethanol, we observed induction of helical structure conformation using CD spectroscopy. Additionally, in SDS, NSP1-CTR shows a conformational change from disordered to ordered, possibly gaining alpha-helix in part. But in the presence of neutral lipid DOPC, a slight change in conformation is observed, which implies the possible role of hydrophobic interaction and electrostatic interaction on the conformational changes of NSP1. Fluorescence-based studies have shown a blue shift and fluorescence quenching in the presence of SDS, TFE, and lipid vesicles. In agreement with these results, fluorescence lifetime and fluorescence anisotropy decay suggest a change in conformational dynamics. The zeta potential studies further validated that the conformational dynamics are primarily because of hydrophobic interaction. These experimental studies were complemented through Molecular Dynamics (MD) simulations, which have shown a good correlation and testifies our experiments. We believe that the intrinsically disordered nature of the NSP1-CTR will have implications for enhanced molecular recognition feature properties of this IDR, which may add disorder to order transition and disorder-based binding promiscuity with its interacting proteins.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"2 ","pages":"Article 100007"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crviro.2021.100007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39122831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shirley L. Smith , Enyia R. Anderson , Cintia Cansado-Utrilla , Tessa Prince , Sean Farrell , Bethaney Brant , Steven Smyth , Peter-John M. Noble , Gina L. Pinchbeck , Nikki Marshall , Larry Roberts , Grant L. Hughes , Alan D. Radford , Edward I. Patterson
{"title":"SARS-CoV-2 neutralising antibodies in dogs and cats in the United Kingdom","authors":"Shirley L. Smith , Enyia R. Anderson , Cintia Cansado-Utrilla , Tessa Prince , Sean Farrell , Bethaney Brant , Steven Smyth , Peter-John M. Noble , Gina L. Pinchbeck , Nikki Marshall , Larry Roberts , Grant L. Hughes , Alan D. Radford , Edward I. Patterson","doi":"10.1016/j.crviro.2021.100011","DOIUrl":"10.1016/j.crviro.2021.100011","url":null,"abstract":"<div><p>Companion animals are susceptible to SARS-CoV-2 infection and sporadic cases of pet infections have occurred in the United Kingdom. Here we present the first large-scale serological survey of SARS-CoV-2 neutralising antibodies in dogs and cats in the UK. Results are reported for 688 sera (454 canine, 234 feline) collected by a large veterinary diagnostic laboratory for routine haematology during three time periods; pre-COVID-19 (January 2020), during the first wave of UK human infections (April–May 2020) and during the second wave of UK human infections (September 2020–February 2021). Both pre-COVID-19 sera and those from the first wave tested negative. However, in sera collected during the second wave, 1.4% (n = 4) of dogs and 2.2% (n = 2) of cats tested positive for neutralising antibodies. The low numbers of animals testing positive suggests pet animals are unlikely to be a major reservoir for human infection in the UK. However, continued surveillance of in-contact susceptible animals should be performed as part of ongoing population health surveillance initiatives.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"2 ","pages":"Article 100011"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crviro.2021.100011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39309843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duo Xu , Mahamaya Biswal , Arrmund Neal , Rong Hai
{"title":"Devil's tools: SARS-CoV-2 antagonists against innate immunity","authors":"Duo Xu , Mahamaya Biswal , Arrmund Neal , Rong Hai","doi":"10.1016/j.crviro.2021.100013","DOIUrl":"https://doi.org/10.1016/j.crviro.2021.100013","url":null,"abstract":"<div><p>The unprecedented Coronavirus pandemic of 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Like other coronaviruses, to establish its infection, SARS-CoV-2 is required to overcome the innate interferon (IFN) response, which is the first line of host defense. SARS-CoV-2 has also developed complex antagonism approaches involving almost all its encoding viral proteins. Here, we summarize our current understanding of these different viral factors and their roles in suppressing IFN responses. Some of them are conserved IFN evasion strategies used by SARS-CoV; others are novel countermeasures only employed by SARS-CoV-2. The filling of gaps in understanding these underlying mechanisms will provide rationale guidance for applying IFN treatment against SARS-CoV-2 infection.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"2 ","pages":"Article 100013"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666478X21000076/pdfft?md5=437ed2336e3b0aaa2d02604b51b58559&pid=1-s2.0-S2666478X21000076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91956910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
X. Qiu, I. Eke, Silas F. Johnson, C. Ding, Yong-Hui Zheng
{"title":"Proteasomal degradation of human SERINC4: A potent host anti-HIV-1 factor that is antagonized by nef","authors":"X. Qiu, I. Eke, Silas F. Johnson, C. Ding, Yong-Hui Zheng","doi":"10.1101/2020.12.07.414888","DOIUrl":"https://doi.org/10.1101/2020.12.07.414888","url":null,"abstract":"The serine incorporator (SERINC) protein family has five paralogous members with 9-11 transmembrane domains. SERINC5 is a potent host restriction factor and antagonized by HIV-1 Nef and two other retroviral accessory proteins via the lysosomal degradation pathway. Here, we investigated human SERINC4 expression and antiviral mechanisms. Unlike its four paralogs, human SERINC4 is subjected to proteasome-mediated turnover, resulting in ~250-fold lower expression than SERINC5. However, when expression was normalized, human SERINC4 restricted HIV-1 replication as effectively as SERINC5, and SERINC4 was also antagonized by Nef via the lysosomal pathway. Although SERINC4 proteins are conserved within primates or rodents, their N-terminal regions are highly variable across species. Interestingly, unlike human SERINC4, murine SERINC4 was stably expressed but had a very poor antiviral activity. We created stable SERINC4 chimeras by replacing the N-terminal region and found that the 1-34 and 35-92 amino acids determine SERINC4 antiviral activity or protein expression, respectively. Using these chimeras, we demonstrate that SERINC4 is incorporated into HIV-1 virions and restricts Tier 1 HIV-1 more effectively than Tier 3 HIV-1. Importantly, SERINC4 increases HIV-1 sensitivity to broadly neutralizing antibodies. Thus, human SERINC4 strongly restricts HIV-1 replication when it is overexpressed, which reflects a potential antiviral activity of this gene product under physiological conditions. Highlights Identification of another potent anti-HIV-1 host factor SERINC4 from the SERINC family Identification of two N-terminal domains that regulate SERINC4 expression and antiviral activity Understanding the natural degradation of human SERINC4 by the proteasomal pathway Understanding the important role of the lysosomal pathway in Nef antagonism of host restriction","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43410428","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":"Publisher Note","authors":"","doi":"10.1016/S2666-478X(20)30006-4","DOIUrl":"10.1016/S2666-478X(20)30006-4","url":null,"abstract":"","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"1 ","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S2666-478X(20)30006-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56894145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xusheng Qiu , Ifeanyichukwu E. Eke , Silas F. Johnson , Chan Ding , Yong-Hui Zheng
{"title":"Proteasomal degradation of human SERINC4: A potent host anti-HIV-1 factor that is antagonized by nef","authors":"Xusheng Qiu , Ifeanyichukwu E. Eke , Silas F. Johnson , Chan Ding , Yong-Hui Zheng","doi":"10.1016/j.crviro.2020.100002","DOIUrl":"10.1016/j.crviro.2020.100002","url":null,"abstract":"<div><p>The serine incorporator (SERINC) protein family has five paralogous members with 9–11 transmembrane domains. SERINC5 is a potent host restriction factor and antagonized by HIV-1 Nef and two other retroviral accessory proteins via the lysosomal degradation pathway. Here, we investigated human SERINC4 expression and antiviral mechanisms. Unlike its four paralogs, human SERINC4 is subjected to proteasome-mediated turnover, resulting in ~250-fold lower expression than SERINC5. However, when expression was normalized, human SERINC4 restricted HIV-1 replication as effectively as SERINC5, and SERINC4 was also antagonized by Nef via the lysosomal pathway. Although SERINC4 proteins are conserved within primates or rodents, their N-terminal regions are highly variable across species. Interestingly, unlike human SERINC4, murine SERINC4 was stably expressed but had a very poor antiviral activity. We created stable SERINC4 chimeras by replacing the N-terminal region and found that the 1–34 and 35–92 amino acids determine SERINC4 antiviral activity or protein expression, respectively. Using these chimeras, we demonstrate that SERINC4 is incorporated into HIV-1 virions and restricts Tier 1 HIV-1 more effectively than Tier 3 HIV-1. Importantly, SERINC4 increases HIV-1 sensitivity to broadly neutralizing antibodies. Thus, human SERINC4 strongly restricts HIV-1 replication when it is overexpressed, which reflects a potential antiviral activity of this gene product under physiological conditions.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"1 ","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crviro.2020.100002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25316849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dicer monitoring in a model filamentous fungus host, Cryphonectria parasitica","authors":"Annisa Aulia , Midori Tabara , Paul Telengech , Toshiyuki Fukuhara , Nobuhiro Suzuki","doi":"10.1016/j.crviro.2020.100001","DOIUrl":"10.1016/j.crviro.2020.100001","url":null,"abstract":"<div><p>The ascomycete <em>Cryphonectria parasitica</em> has served as a model filamentous fungus for studying virus host interactions because of its susceptibility to diverse viruses, its genetic manipulability and the availability of many biological and molecular tools. <em>Cryphonectria prasitica</em> is known to activate antiviral RNA silencing upon infection by some viruses via transcriptional up-regulation of key RNA silencing genes. Here, utilizing a newly developed GFP-based reporter system to monitor dicer-like 2 (<em>dcl2</em>) transcript levels, we show different levels of antiviral RNA silencing activation by different viruses. Some viruses such as mycoreovirus 1, a suppressor-lacking mutant of Cryphonectria hypovirus 1 (CHV1-Δp69) and Rosellinia necatrix partitivirus 11 (RnPV11) highly induced RNA silencing, while others such as CHV3, Rosellinia necatrix victorivirus 1 and RnPV19 did not. There was considerable variation in <em>dcl2</em> induction by different members within the family <em>Hypoviridae</em> with positive-sense single-stranded RNA genomes or <em>Partitiviridae</em> with double-stranded RNA genomes. Northern blotting and an <em>in vitro</em> Dicer assay developed recently by us using mycelial homogenates validated the reporter assay results for several representative virus strains. Taken together, this study represents a development in the monitoring of Dicer activity in virus-infected <em>C. parasitica</em>.</p></div>","PeriodicalId":72755,"journal":{"name":"Current research in virological science","volume":"1 ","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.crviro.2020.100001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"110077053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}