Pub Date : 2021-01-01Epub Date: 2021-03-01DOI: 10.1159/000513685
Kathy Jackson, Margaret Littlejohn, Ed Gane, Stephen Locarnini
Hepatitis delta virus (HDV) is considered a satellite virus that requires hepatitis B virus surface antigen for infectivity. HDV is endemic in some Pacific Island (PI) countries, including Kiribati and Nauru, with a unique genotype 1, "Pacific clade." The aims of this study were to determine the HDV genotypes in New Zealand and investigate the link of strains to other PI countries and the rest of the world through phylogenetics. Sequencing and phylogenetic analyses were performed on 16 HDV-positive serum samples from 14 individuals collected between 2009 and 2014 at Auckland Hospital. Thirteen of 14 strains were confirmed as genotype 1 and 1 was genotype 5. Eleven of the 13 genotype 1 strains clustered with the Pacific clade. These were isolated from subjects born in Samoa, Kiribati, Tuvalu, and Niue. Another genotype 1 strain isolated from a Maori health-care worker clustered most closely with a European strain. There was an African genotype 1 and genotype 5 from African-born subjects with HIV coinfection. This study supports the probable transmission of HDV Pacific clade around the PI from Micronesia to Polynesia. The data also confirm the need to screen hepatitis B surface antigen-positive individuals for HDV.
{"title":"Molecular Phylogenetics of Hepatitis D Virus in New Zealand and the Implications for Pacific Island Countries.","authors":"Kathy Jackson, Margaret Littlejohn, Ed Gane, Stephen Locarnini","doi":"10.1159/000513685","DOIUrl":"https://doi.org/10.1159/000513685","url":null,"abstract":"<p><p>Hepatitis delta virus (HDV) is considered a satellite virus that requires hepatitis B virus surface antigen for infectivity. HDV is endemic in some Pacific Island (PI) countries, including Kiribati and Nauru, with a unique genotype 1, \"Pacific clade.\" The aims of this study were to determine the HDV genotypes in New Zealand and investigate the link of strains to other PI countries and the rest of the world through phylogenetics. Sequencing and phylogenetic analyses were performed on 16 HDV-positive serum samples from 14 individuals collected between 2009 and 2014 at Auckland Hospital. Thirteen of 14 strains were confirmed as genotype 1 and 1 was genotype 5. Eleven of the 13 genotype 1 strains clustered with the Pacific clade. These were isolated from subjects born in Samoa, Kiribati, Tuvalu, and Niue. Another genotype 1 strain isolated from a Maori health-care worker clustered most closely with a European strain. There was an African genotype 1 and genotype 5 from African-born subjects with HIV coinfection. This study supports the probable transmission of HDV Pacific clade around the PI from Micronesia to Polynesia. The data also confirm the need to screen hepatitis B surface antigen-positive individuals for HDV.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"102-107"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25417379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Serum osteopontin (OPN) concentrations were found to be significantly increased in patients infected with hepatitis B virus (HBV) and patients with hepatocellular carcinoma (HCC).
Objective: The aim of this study was to determine the association among HCC, OPN, and HBV.
Methods: Two hundred and forty-one subjects were recruited and divided into 6 groups: healthy controls, asymptomatic HBsAg carriers, HBsAg (-) patients with other tumors, HBsAg (+) chronic liver disease patients, HBsAg (+) patients with HCC, and HBsAg (-) patients with HCC or liver cirrhosis (LC). Serum concentrations of OPN and HBsAg were measured and analyzed.
Results: OPN concentrations in the HBsAg (+) HCC group were significantly higher than the healthy control group and the HBsAg (-) patients with other cancers (both p = 0.0001). The OPN concentrations of the HBsAg (-) patients with HCC or LC also did not differ significantly from those of the healthy control group (p = 0.075). There is a correlation between the titer of HBsAg and concentrations of OPN in all 3 HBsAg (+) groups (all p values <0.05).
Conclusions: Infection with HBV may increase the serum concentrations of OPN. The association of OPN and HCC may be not attributable to tumor development per se but, rather, to HBV infection.
{"title":"Infection with Hepatitis B Virus May Increase the Serum Concentrations of Osteopontin.","authors":"Hua-Bing Liu, Qin-Yan Chen, Xue-Yan Wang, Lu-Juan Zhang, Li-Ping Hu, Tim J Harrison, Chao Wang, Zhong-Liao Fang","doi":"10.1159/000513687","DOIUrl":"10.1159/000513687","url":null,"abstract":"<p><strong>Background: </strong>Serum osteopontin (OPN) concentrations were found to be significantly increased in patients infected with hepatitis B virus (HBV) and patients with hepatocellular carcinoma (HCC).</p><p><strong>Objective: </strong>The aim of this study was to determine the association among HCC, OPN, and HBV.</p><p><strong>Methods: </strong>Two hundred and forty-one subjects were recruited and divided into 6 groups: healthy controls, asymptomatic HBsAg carriers, HBsAg (-) patients with other tumors, HBsAg (+) chronic liver disease patients, HBsAg (+) patients with HCC, and HBsAg (-) patients with HCC or liver cirrhosis (LC). Serum concentrations of OPN and HBsAg were measured and analyzed.</p><p><strong>Results: </strong>OPN concentrations in the HBsAg (+) HCC group were significantly higher than the healthy control group and the HBsAg (-) patients with other cancers (both p = 0.0001). The OPN concentrations of the HBsAg (-) patients with HCC or LC also did not differ significantly from those of the healthy control group (p = 0.075). There is a correlation between the titer of HBsAg and concentrations of OPN in all 3 HBsAg (+) groups (all p values <0.05).</p><p><strong>Conclusions: </strong>Infection with HBV may increase the serum concentrations of OPN. The association of OPN and HCC may be not attributable to tumor development per se but, rather, to HBV infection.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 3","pages":"126-134"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25491948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aichi virus 1 (AiV-1) has been proposed as a causative agent of human gastroenteritis. In this study, raw, decanted, and treated wastewater samples from a wastewater treatment plant in an urban area of Dakar, Senegal, were collected. AiV-1 was detected in raw (70%, 14/20), decanted (68.4%, 13/19), and treated (59.3%, 16/27) samples, revealing a noticeable resistance of AiV-1 to chlorine-based treatment. Phylogenetic analysis revealed that all sequences clustered within genotype B. Our study presents the first report on the detection of AiV-1 in the environment of Dakar and constitutes indirect evidence of virus circulation in the population.
{"title":"Prevalence and Genetic Diversity of Aichi Virus 1 from Urban Wastewater in Senegal.","authors":"Ousmane Kebe, Maria-Dolores Fernandez-Garcia, Amary Fall, Hamet Dia, Maxime Bidalot, Katia Ambert-Balay, Kader Ndiaye","doi":"10.1159/000512130","DOIUrl":"https://doi.org/10.1159/000512130","url":null,"abstract":"<p><p>Aichi virus 1 (AiV-1) has been proposed as a causative agent of human gastroenteritis. In this study, raw, decanted, and treated wastewater samples from a wastewater treatment plant in an urban area of Dakar, Senegal, were collected. AiV-1 was detected in raw (70%, 14/20), decanted (68.4%, 13/19), and treated (59.3%, 16/27) samples, revealing a noticeable resistance of AiV-1 to chlorine-based treatment. Phylogenetic analysis revealed that all sequences clustered within genotype B. Our study presents the first report on the detection of AiV-1 in the environment of Dakar and constitutes indirect evidence of virus circulation in the population.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"96-101"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38748927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01Epub Date: 2021-02-24DOI: 10.1159/000512956
Bahar Sadegh Ehdaei, Ahmad Pirouzmand, Mehdi Shabani, Arezoo Mirzaei, Sharareh Moghim
Introduction: Herpes simplex viruses (HSVs) are widely distributed in the human population. HSV type 1 (HSV-1) is responsible for a spectrum of diseases, ranging from gingivostomatitis to keratoconjunctivitis, and encephalitis. The HSVs establish latent infections in nerve cells, and recurrences are common. Their frequent reactivation in elderly and immunosuppressed patients causes serious health complications.
Objectives: Due to the growing resistance to its main drug, acyclovir, alternative treatments with different mechanisms of action are required. MicroRNAs regulate host and viral gene expression posttranscriptionally. Previous studies reported that mir-101-2 expression has widely participated in the regulation of HSV-1 replication. In this study, we investigate the effect of hsa-miR-101-1 in the replication of HSV-1.
Methods: We found that transfection of miR-101-1 into HeLa cells could reduce effectively HSV-1 replication using plaque assay and real-time PCR methods.
Results: We showed that overexpression of miR-10-1 produced less viral progeny and manifested a weaker cytopathic effect, without affecting cell viability.
Discussion/conclusion: This result can give us new insights into the control of HSV-1 infections.
{"title":"Cellular miR-101-1 Reduces Efficiently the Replication of HSV-1 in HeLa Cells.","authors":"Bahar Sadegh Ehdaei, Ahmad Pirouzmand, Mehdi Shabani, Arezoo Mirzaei, Sharareh Moghim","doi":"10.1159/000512956","DOIUrl":"https://doi.org/10.1159/000512956","url":null,"abstract":"<p><strong>Introduction: </strong>Herpes simplex viruses (HSVs) are widely distributed in the human population. HSV type 1 (HSV-1) is responsible for a spectrum of diseases, ranging from gingivostomatitis to keratoconjunctivitis, and encephalitis. The HSVs establish latent infections in nerve cells, and recurrences are common. Their frequent reactivation in elderly and immunosuppressed patients causes serious health complications.</p><p><strong>Objectives: </strong>Due to the growing resistance to its main drug, acyclovir, alternative treatments with different mechanisms of action are required. MicroRNAs regulate host and viral gene expression posttranscriptionally. Previous studies reported that mir-101-2 expression has widely participated in the regulation of HSV-1 replication. In this study, we investigate the effect of hsa-miR-101-1 in the replication of HSV-1.</p><p><strong>Methods: </strong>We found that transfection of miR-101-1 into HeLa cells could reduce effectively HSV-1 replication using plaque assay and real-time PCR methods.</p><p><strong>Results: </strong>We showed that overexpression of miR-10-1 produced less viral progeny and manifested a weaker cytopathic effect, without affecting cell viability.</p><p><strong>Discussion/conclusion: </strong>This result can give us new insights into the control of HSV-1 infections.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"88-95"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25400802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01Epub Date: 2021-02-11DOI: 10.1159/000512135
Yueqi Yin, Ying Zhou, Jing Lu, Hongxiong Guo, Jianshuang Chen, Yan Xuan, Defu Yuan, Haiyang Hu, Xiaoqin Xu, Gengfeng Fu, Bei Wang
Introduction: A large number of unique recombinant forms have been found in China in recent years. This study aimed to report on a cluster of novel HIV-1 recombinants.
Methods: We constructed phylogenetic trees using the maximum likelihood (ML) method with 1,000 bootstrap replicates in IQ-TREE 1.6.8 software and determined recombination break points using SimPlot 3.5.1.
Results: Overall, 9 near-full-length genome (NFLG) sequences were reported in this study, including 1 circulation recombinant form (CRF)01_AE NFLG sequence and 8 highly similar novel HIV-1 second-generation recombinants composed of CRF01_AE and CRF07_BC (CRF105_0107) isolated from a cluster HIV-positive male subjects infected among men who have sex with men (MSM) in Nanjing, eastern China. The phylogenetic analysis of NFLG showed 1 sequence named "nj16" to have at least 11 breakpoints inner virus and 7 other sequences to have at least 10 breakpoints inner virus. Our findings further showed as follows: first, this is the first time that a cluster of novel CRF105_0107 HIV-1 strains were identified among MSM in Nanjing, Jiangsu. Second, the Chinese "4a" cluster of CRF01_AE which mainly circulating in northern China has spread in Jiangsu for more than 15 years. Third, HIV-1 recombination events were active in Nanjing city, and novel recombinants could spread rapidly through some small-scale transmission networks.
Conclusion: The continued emergence of novel recombinant HIV-1 strains in Nanjing suggests dynamics and complexity in the HIV epidemic among MSM in Jiangsu province. Further investigations and molecular epidemiological research should be taken to monitor and understand transmission networks among MSM.
{"title":"First Detection of a Cluster Novel HIV-1 Second-Generation Recombinant (CRF01_AE/CRF07_BC) among Men Who Have Sex with Men in Nanjing, Eastern China.","authors":"Yueqi Yin, Ying Zhou, Jing Lu, Hongxiong Guo, Jianshuang Chen, Yan Xuan, Defu Yuan, Haiyang Hu, Xiaoqin Xu, Gengfeng Fu, Bei Wang","doi":"10.1159/000512135","DOIUrl":"https://doi.org/10.1159/000512135","url":null,"abstract":"<p><strong>Introduction: </strong>A large number of unique recombinant forms have been found in China in recent years. This study aimed to report on a cluster of novel HIV-1 recombinants.</p><p><strong>Methods: </strong>We constructed phylogenetic trees using the maximum likelihood (ML) method with 1,000 bootstrap replicates in IQ-TREE 1.6.8 software and determined recombination break points using SimPlot 3.5.1.</p><p><strong>Results: </strong>Overall, 9 near-full-length genome (NFLG) sequences were reported in this study, including 1 circulation recombinant form (CRF)01_AE NFLG sequence and 8 highly similar novel HIV-1 second-generation recombinants composed of CRF01_AE and CRF07_BC (CRF105_0107) isolated from a cluster HIV-positive male subjects infected among men who have sex with men (MSM) in Nanjing, eastern China. The phylogenetic analysis of NFLG showed 1 sequence named \"nj16\" to have at least 11 breakpoints inner virus and 7 other sequences to have at least 10 breakpoints inner virus. Our findings further showed as follows: first, this is the first time that a cluster of novel CRF105_0107 HIV-1 strains were identified among MSM in Nanjing, Jiangsu. Second, the Chinese \"4a\" cluster of CRF01_AE which mainly circulating in northern China has spread in Jiangsu for more than 15 years. Third, HIV-1 recombination events were active in Nanjing city, and novel recombinants could spread rapidly through some small-scale transmission networks.</p><p><strong>Conclusion: </strong>The continued emergence of novel recombinant HIV-1 strains in Nanjing suggests dynamics and complexity in the HIV epidemic among MSM in Jiangsu province. Further investigations and molecular epidemiological research should be taken to monitor and understand transmission networks among MSM.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"81-87"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25357867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01Epub Date: 2021-03-18DOI: 10.1159/000513965
Ángel L Álvarez, Francisco Parra
In a recent JVI paper by Urban and Luttermann [1], a truncated version of VP1 precursor (tLC-VP1) synthesized directly from the genomic RNA (gRNA) was detected for the first time for Feline calicivirus (FCV). Through a series of comprehensive reverse genetics experiments using 3DPol/LC-cleavage mutants, RIPA, luciferase reporter assays and deletion mutants, the authors demonstrated translational activity leading to tLC-VP1 synthesis starting at AUG codon 86, which they claim to be the second start codon within the whole LC-VP1 sequence. The authors suggested that a novel, scanning-independent, rather unknown translation initiation mechanism may be responsible for tLC-VP1 synthesis and identified specific sequences upstream of M86 that appear to be important for its efficiency. For example, in a reporter assay, the S3S mutant, lacking a stem-loop naturally occurring close to the LC-VP1 first AUG (M1), showed a dramatically decreased luciferase expression due to impaired translation initiation at M86. Furthermore, in a multiple-step growth assay, the S3S mutant showed decreased titers at early points of the curve, compared to wild-type FCV, though all assayed viruses reached similar end point titers. Based on these findings, the authors speculate that tLC-VP1 has a role during early phases of virus replication and claim that “all caliciviruses express VP1 from the gRNA” because it is essential and required early upon infection. We expected that the authors discussed the well-established fact that all caliciviruses encapsidate the subgenomic RNA (sgRNA) within the virions [2, 3], that is readily translated upon infection and the biological significance of producing a rather redundant tLC-VP1 in this context. The authors based their work on the sequence of FCV 2024 vaccine strain (GenBank AF479590.1) that contain no additional methionine residue between M1 and M86. However, a close look at other GenBank FCV sequences reveals that most FCV strains do possess another inframe AUG start codon within the LC-VP1 sequence at position 38 (M38), which has been overlooked in this work (Fig. 1a). In addition, when we compared the LCVP1 sequence from FCV strain Urbana with those of several members of the Vesivirus genus we found no inframe AUG start codon between the first ORF2 AUG (M1) and the putative proteolytic cleavage site responsible for LC excision and release of mature VP1, except for Allston calicivirus (M122, M134, M141) and SMSV-8
{"title":"Truncated Precursor of Feline calicivirus Major Capsid Protein: A Product Relevant for Replication, or an Aberrant Translation Artifact?","authors":"Ángel L Álvarez, Francisco Parra","doi":"10.1159/000513965","DOIUrl":"https://doi.org/10.1159/000513965","url":null,"abstract":"In a recent JVI paper by Urban and Luttermann [1], a truncated version of VP1 precursor (tLC-VP1) synthesized directly from the genomic RNA (gRNA) was detected for the first time for Feline calicivirus (FCV). Through a series of comprehensive reverse genetics experiments using 3DPol/LC-cleavage mutants, RIPA, luciferase reporter assays and deletion mutants, the authors demonstrated translational activity leading to tLC-VP1 synthesis starting at AUG codon 86, which they claim to be the second start codon within the whole LC-VP1 sequence. The authors suggested that a novel, scanning-independent, rather unknown translation initiation mechanism may be responsible for tLC-VP1 synthesis and identified specific sequences upstream of M86 that appear to be important for its efficiency. For example, in a reporter assay, the S3S mutant, lacking a stem-loop naturally occurring close to the LC-VP1 first AUG (M1), showed a dramatically decreased luciferase expression due to impaired translation initiation at M86. Furthermore, in a multiple-step growth assay, the S3S mutant showed decreased titers at early points of the curve, compared to wild-type FCV, though all assayed viruses reached similar end point titers. Based on these findings, the authors speculate that tLC-VP1 has a role during early phases of virus replication and claim that “all caliciviruses express VP1 from the gRNA” because it is essential and required early upon infection. We expected that the authors discussed the well-established fact that all caliciviruses encapsidate the subgenomic RNA (sgRNA) within the virions [2, 3], that is readily translated upon infection and the biological significance of producing a rather redundant tLC-VP1 in this context. The authors based their work on the sequence of FCV 2024 vaccine strain (GenBank AF479590.1) that contain no additional methionine residue between M1 and M86. However, a close look at other GenBank FCV sequences reveals that most FCV strains do possess another inframe AUG start codon within the LC-VP1 sequence at position 38 (M38), which has been overlooked in this work (Fig. 1a). In addition, when we compared the LCVP1 sequence from FCV strain Urbana with those of several members of the Vesivirus genus we found no inframe AUG start codon between the first ORF2 AUG (M1) and the putative proteolytic cleavage site responsible for LC excision and release of mature VP1, except for Allston calicivirus (M122, M134, M141) and SMSV-8","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"108-110"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25491901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01Epub Date: 2021-01-15DOI: 10.1159/000513686
Muhammad Tahir Khan, Muhammad Irfan, Hina Ahsan, Abrar Ahmed, Aman Chandra Kaushik, Anwar Sheed Khan, Sathishkumar Chinnasamy, Arif Ali, Dong-Qing Wei
Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases.
Summary: In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (Mpro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.
{"title":"Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets.","authors":"Muhammad Tahir Khan, Muhammad Irfan, Hina Ahsan, Abrar Ahmed, Aman Chandra Kaushik, Anwar Sheed Khan, Sathishkumar Chinnasamy, Arif Ali, Dong-Qing Wei","doi":"10.1159/000513686","DOIUrl":"https://doi.org/10.1159/000513686","url":null,"abstract":"<p><strong>Background: </strong>The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases.</p><p><strong>Summary: </strong>In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (Mpro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"55-68"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38829971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To investigate the relationship between hematologic tumors and Epstein-Barr virus (EBV)-encoded small noncoding RNA (EBER) variations as well as latent membrane protein 1 (LMP1) variations.
Methods: Patients with leukemia and myelodysplastic syndrome (MDS) were selected as subjects. Genotypes 1/2 and genotypes F/f were analyzed using the nested PCR technology, while EBER and LMP1 subtypes were analyzed by the nested PCR and DNA sequencing.
Results: Type 1 was more dominant than type 2, found in 59 out of 82 (72%) leukemia and in 31 out of 35 (88.6%) MDS, while type F was more prevalent than type f in leukemia (83/85, 97.6%) and MDS (29/31, 93.5%) samples. The distribution of EBV genotypes 1/2 was not significantly different among leukemia, MDS, and healthy donor groups, neither was that of EBV genotypes F/f. EB-6m prototype was the dominant subtype of EBER in leukemia and MDS (73.2% [30/41] and 83.3% [10/12], respectively). The frequency of EB-6m was lower than that of healthy people (96.7%, 89/92), and the difference was significant (p < 0.05). China 1 subtype was the dominant subtype of LMP1 in leukemia and MDS (70% [28/40] and 90% [9/10], respectively), and there was no significant difference in the distribution of LMP1 subtypes among the 3 groups (p > 0.05).
Conclusion: The distribution of EBV 1/2, F/f, EBER, and LMP1 subtypes in leukemia and MDS was similar to that in the background population in Northern China, which means that these subtypes may be rather region-restricted but not associated with leukemia and MDS pathogenesis.
{"title":"Sequence Variations of Epstein-Barr Virus-Encoded Small Noncoding RNA and Latent Membrane Protein 1 in Hematologic Tumors in Northern China.","authors":"Hai-Yu Wang, Lingling Sun, Ping Li, Wen Liu, Zhong-Guang Zhang, Bing Luo","doi":"10.1159/000510398","DOIUrl":"https://doi.org/10.1159/000510398","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the relationship between hematologic tumors and Epstein-Barr virus (EBV)-encoded small noncoding RNA (EBER) variations as well as latent membrane protein 1 (LMP1) variations.</p><p><strong>Methods: </strong>Patients with leukemia and myelodysplastic syndrome (MDS) were selected as subjects. Genotypes 1/2 and genotypes F/f were analyzed using the nested PCR technology, while EBER and LMP1 subtypes were analyzed by the nested PCR and DNA sequencing.</p><p><strong>Results: </strong>Type 1 was more dominant than type 2, found in 59 out of 82 (72%) leukemia and in 31 out of 35 (88.6%) MDS, while type F was more prevalent than type f in leukemia (83/85, 97.6%) and MDS (29/31, 93.5%) samples. The distribution of EBV genotypes 1/2 was not significantly different among leukemia, MDS, and healthy donor groups, neither was that of EBV genotypes F/f. EB-6m prototype was the dominant subtype of EBER in leukemia and MDS (73.2% [30/41] and 83.3% [10/12], respectively). The frequency of EB-6m was lower than that of healthy people (96.7%, 89/92), and the difference was significant (p < 0.05). China 1 subtype was the dominant subtype of LMP1 in leukemia and MDS (70% [28/40] and 90% [9/10], respectively), and there was no significant difference in the distribution of LMP1 subtypes among the 3 groups (p > 0.05).</p><p><strong>Conclusion: </strong>The distribution of EBV 1/2, F/f, EBER, and LMP1 subtypes in leukemia and MDS was similar to that in the background population in Northern China, which means that these subtypes may be rather region-restricted but not associated with leukemia and MDS pathogenesis.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 2","pages":"69-80"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25468516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Three newly discovered viruses have been recently described in diarrheal patients: Cosavirus (CosV) and Salivirus (SalV), 2 picornaviruses, and bufavirus (BuV), a parvovirus. The detection rate and the role of these viruses remain to be established in acute gastroenteritis (AGE) in diarrheal Italian infants. From November 2016 to November 2017, stool samples were collected from 160 children <5 years old suffering from AGE and attending the Children's Hospital in Turin, Italy. During the study period, 1 (0.5%) sample was positive for 1 of the 3 investigated viruses: 0 (0%) CosV, 1 (0.5%) SalV, and 0 (0%) BuV, whereas 42 (26.0%) children were infected with rotavirus and 2 (1%) with adenovirus. No mixed infections involving the 3 viruses were found. Although these viruses are suspected to be responsible for AGE in children, our data showed that this association was uncertain. Therefore, further studies with large cohorts of healthy and diarrheal children will be needed to evaluate their clinical role in AGE.
{"title":"Bufavirus, Cosavirus, and Salivirus in Diarrheal Italian Infants.","authors":"Valentina Daprà, Ilaria Galliano, Paola Montanari, Elena Zaniol, Cristina Calvi, Carla Alliaudi, Massimiliano Bergallo","doi":"10.1159/000514384","DOIUrl":"https://doi.org/10.1159/000514384","url":null,"abstract":"<p><p>Three newly discovered viruses have been recently described in diarrheal patients: Cosavirus (CosV) and Salivirus (SalV), 2 picornaviruses, and bufavirus (BuV), a parvovirus. The detection rate and the role of these viruses remain to be established in acute gastroenteritis (AGE) in diarrheal Italian infants. From November 2016 to November 2017, stool samples were collected from 160 children <5 years old suffering from AGE and attending the Children's Hospital in Turin, Italy. During the study period, 1 (0.5%) sample was positive for 1 of the 3 investigated viruses: 0 (0%) CosV, 1 (0.5%) SalV, and 0 (0%) BuV, whereas 42 (26.0%) children were infected with rotavirus and 2 (1%) with adenovirus. No mixed infections involving the 3 viruses were found. Although these viruses are suspected to be responsible for AGE in children, our data showed that this association was uncertain. Therefore, further studies with large cohorts of healthy and diarrheal children will be needed to evaluate their clinical role in AGE.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"64 3","pages":"165-168"},"PeriodicalIF":4.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25532104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravali Thota, Vishweshwar Kumar Ganji, Sharanya Machanagari, Narasimha Reddy Yella, Bhagyalakshmi Buddala, Krishnajyothi Yadlapati, P P Rao, Sushila Maan, Narender S Maan, Divakar Hemadri, Karam Pal Singh, Kalyani Putty
Introduction: Bluetongue disease is an economically important viral disease of livestock caused by bluetongue virus (BTV) having multiple serotypes. It belongs to the genus Orbivirus of family Reoviridae and subfamily Sedoreovirinae. The genome of BTV is 10 segmented dsRNA that codes for 7 structural and 4 nonstructural proteins, of which VP2 was reported to be serotype-specific and a major antigenic determinant.
Objective: It is important to know the circulating serotypes in a particular geographical location for effective control of the disease. The present study unravels the molecular evolution of the circulating BTV serotypes during 2014-2018 in Telangana and Andhra Pradesh states of India.
Methods: Multiple sequence alignment with available BTV serotypes in GenBank and phylogenetic analysis were performed for the partial VP2 sequences of major circulating BTV serotypes during the study period.
Results: The multiple sequence alignment of circulating serotypes with respective reference isolates revealed variations in antigenic VP2. The phylogenetic analysis revealed that the major circulating serotypes were grouped into eastern topotypes (BTV-1, BTV-2, BTV-4, and BTV-16) and Western topotypes (BTV-5, BTV-12, and BTV-24).
Conclusion: Our study strengthens the need for development of an effective vaccine, which can induce the immune response for a range of serotypes within and in between topotypes.
{"title":"VP2 Gene-Based Molecular Evolutionary Patterns of Major Circulating Bluetongue Virus Serotypes Isolated during 2014-2018 from Telangana and Andhra Pradesh States of India.","authors":"Ravali Thota, Vishweshwar Kumar Ganji, Sharanya Machanagari, Narasimha Reddy Yella, Bhagyalakshmi Buddala, Krishnajyothi Yadlapati, P P Rao, Sushila Maan, Narender S Maan, Divakar Hemadri, Karam Pal Singh, Kalyani Putty","doi":"10.1159/000512131","DOIUrl":"10.1159/000512131","url":null,"abstract":"<p><strong>Introduction: </strong>Bluetongue disease is an economically important viral disease of livestock caused by bluetongue virus (BTV) having multiple serotypes. It belongs to the genus Orbivirus of family Reoviridae and subfamily Sedoreovirinae. The genome of BTV is 10 segmented dsRNA that codes for 7 structural and 4 nonstructural proteins, of which VP2 was reported to be serotype-specific and a major antigenic determinant.</p><p><strong>Objective: </strong>It is important to know the circulating serotypes in a particular geographical location for effective control of the disease. The present study unravels the molecular evolution of the circulating BTV serotypes during 2014-2018 in Telangana and Andhra Pradesh states of India.</p><p><strong>Methods: </strong>Multiple sequence alignment with available BTV serotypes in GenBank and phylogenetic analysis were performed for the partial VP2 sequences of major circulating BTV serotypes during the study period.</p><p><strong>Results: </strong>The multiple sequence alignment of circulating serotypes with respective reference isolates revealed variations in antigenic VP2. The phylogenetic analysis revealed that the major circulating serotypes were grouped into eastern topotypes (BTV-1, BTV-2, BTV-4, and BTV-16) and Western topotypes (BTV-5, BTV-12, and BTV-24).</p><p><strong>Conclusion: </strong>Our study strengthens the need for development of an effective vaccine, which can induce the immune response for a range of serotypes within and in between topotypes.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"1-8"},"PeriodicalIF":4.6,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38765601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}