Research

12 pages, 2403 KiB

Open AccessArticle

Combination of Oncolytic Measles Virus and Ursolic Acid Synergistically Induces Oncolysis of Hepatocellular Carcinoma Cells

by Ching-Hsuan Liu, Chen-Jei Tai, Yu-Ting Kuo, Shen-Shong Chang and Liang-Tzung Lin

Viruses 2023, 15(6), 1294; https://doi.org/10.3390/v15061294 - 31 May 2023

Cited by 2 | Viewed by 1903

Abstract

Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules [...] Read more.

Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules merits further exploration. In this study, we combined oncolytic measles virus (MV) with the natural triterpenoid compound ursolic acid (UA) and evaluated their combination effect against HCC cells, including those harboring hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. We found that the combination of MV and UA synergistically induced more cell death in Huh-7 HCC cells through enhanced apoptosis. In addition, increased oxidative stress and loss of mitochondrial potential were observed in the treated cells, indicating dysregulation of the mitochondria-dependent pathway. Similar synergistic cytotoxic effects were also found in HCC cells harboring HBV or HCV genomes. These findings underscore the potential of oncolytic MV and UA combination for further development as a treatment strategy for HCC. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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15 pages, 578 KiB

Open AccessArticle

Human Papillomavirus Infections and Increased Risk of Incident Osteoporosis: A Nationwide Population-Based Cohort Study

by Kevin Sheng-Kai Ma, Ning-Chien Chin, Ting-Yu Tu, Yao-Cheng Wu, Hei-Tung Yip, James Cheng-Chung Wei and Ren-in Chang

Viruses 2023, 15(4), 1021; https://doi.org/10.3390/v15041021 - 21 Apr 2023

Cited by 1 | Viewed by 1511

Abstract

Patients with viral infections are susceptible to osteoporosis. This cohort study investigated the correlation between human papillomavirus (HPV) infections and the risk of osteoporosis via 12,936 patients with new-onset HPV infections and propensity score-matched non-HPV controls enrolled in Taiwan. The primary endpoint was [...] Read more.

Patients with viral infections are susceptible to osteoporosis. This cohort study investigated the correlation between human papillomavirus (HPV) infections and the risk of osteoporosis via 12,936 patients with new-onset HPV infections and propensity score-matched non-HPV controls enrolled in Taiwan. The primary endpoint was incident osteoporosis following HPV infections. Cox proportional hazards regression analysis and the Kaplan-Meier method was used to determine the effect of HPV infections on the risk of osteoporosis. Patients with HPV infections presented with a significantly high risk of osteoporosis (adjusted hazard ratio, aHR = 1.32, 95% CI = 1.06–1.65) after adjusting for sex, age, comorbidities and co-medications. Subgroup analysis provided that populations at risk of HPV-associated osteoporosis were females (aHR = 1.33; 95% CI = 1.04–1.71), those aged between 60 and 80 years (aHR = 1.45, 95% CI = 1.01–2.08 for patients aged 60–70; aHR = 1.51; 95% CI = 1.07–2.12 for patients aged 70–80), and patients with long-term use of glucocorticoids (aHR = 2.17; 95% CI = 1.11–4.22). HPV-infected patients who did not receive treatments for HPV infections were at a greater risk (aHR = 1.40; 95% CI = 1.09–1.80) of osteoporosis, while the risk of osteoporosis in those who received treatments for HPV infections did not reach statistical significance (aHR = 1.14; 95% CI = 0.78–1.66). Patients with HPV infections presented with a high risk of subsequent osteoporosis. Treatments for HPV infections attenuated the risk of HPV-associated osteoporosis. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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11 pages, 908 KiB

Open AccessArticle

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients

by Wei-Chen Lee, Hao-Chien Hung, Jin-Chiao Lee, Chung-Guei Huang, Po-Wei Huang, Po-Wen Gu, Yu-Chao Wang, Chih-Hsien Cheng, Tsung-Han Wu, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou and Kun-Ming Chan

Viruses 2023, 15(3), 678; https://doi.org/10.3390/v15030678 - 04 Mar 2023

Cited by 3 | Viewed by 1458

Abstract

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for [...] Read more.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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13 pages, 842 KiB

Open AccessArticle

Risk Factors for Influenza-Induced Exacerbations and Mortality in Non-Cystic Fibrosis Bronchiectasis

by Hung-Yu Huang, Chun-Yu Lo, Fu-Tsai Chung, Yu-Tung Huang, Po-Chuan Ko, Chang-Wei Lin, Yu-Chen Huang, Kian Fan Chung and Chun-Hua Wang

Viruses 2023, 15(2), 537; https://doi.org/10.3390/v15020537 - 14 Feb 2023

Cited by 3 | Viewed by 1969

Abstract

Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the [...] Read more.

Influenza infection is a cause of exacerbations in patients with chronic pulmonary diseases. The aim of this study was to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. Using the Chang Gung Research Database, we identified patients with bronchiectasis and influenza-related infection (ICD-9-CM 487 and anti-viral medicine) between 2008 and 2017. The main outcomes were influenza-related hospitalization and in-hospital mortality rate. Eight hundred sixty-five patients with bronchiectasis and influenza infection were identified. Five hundred thirty-six (62%) patients with bronchiectasis were hospitalized for influenza-related infection and 118 (22%) patients had respiratory failure. Compared to the group only seen in clinic, the hospitalization group was older, with more male patients, a lower FEV_1, higher bronchiectasis aetiology comorbidity index (BACI), and more acute exacerbations in the previous year. Co-infections were evident in 55.6% of hospitalized patients, mainly caused by Pseudomonas aeruginosa (15%), fungus (7%), and Klebsiella pneumoniae (6%). The respiratory failure group developed acute kidney injury (36% vs. 16%; p < 0.001), and shock (47% vs. 6%; p < 0.001) more often than influenza patients without respiratory failure. The overall mortality rate was 10.8% and the respiratory failure group exhibited significantly higher in-hospital mortality rates (27.1% vs. 6.2%; p < 0.001). Age, BACI, and previous exacerbations were independently associated with influenza-related hospitalization. Age, presence of shock, and low platelet counts were associated with increased hospital mortality. Influenza virus caused severe exacerbation in bronchiectasis, especially in those who were older and who had high BACI scores and previous exacerbations. A high risk of respiratory failure and mortality were observed in influenza-related hospitalization in bronchiectasis. We highlight the importance of preventing or treating influenza infection in bronchiectasis. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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15 pages, 1570 KiB

Open AccessArticle

Genetic Characteristics of Measles Viruses Isolated in Taiwan between 2015 and 2020

by Wen-Yueh Cheng, Bao-Shen Chen, Hsiao-Chi Wang and Ming-Tsan Liu

Viruses 2023, 15(1), 211; https://doi.org/10.3390/v15010211 - 12 Jan 2023

Viewed by 1519

Abstract

A genetic analysis of circulating measles virus (MeV) provides strong evidence of an interruption in endemic measles and supports the elimination status of this disease. This study investigated 219 MeVs isolated between 2015 and 2020. Based on the 450 nucleotide sequences of the [...] Read more.

A genetic analysis of circulating measles virus (MeV) provides strong evidence of an interruption in endemic measles and supports the elimination status of this disease. This study investigated 219 MeVs isolated between 2015 and 2020. Based on the 450 nucleotide sequences of the nucleoprotein gene (N-450), three genotypes of the H1, D8 and B3 with 8, 18 and 6 different N-450 sequences, respectively, were identified. The H1 genotype virus has not circulated in Taiwan since 2017, and the D8 and B3 genotype MeVs became dominant between 2018 and 2019. Different D8 genotype variants were imported from neighboring countries, and the majority of MeV variants were detected only for a short period. However, MVs/Gir Somnath.IND/42.16[D8], a named strain designated by the World Health Organization (WHO), was detected over 2 years. To explore whether the endemic transmission of measles has been underestimated, another sequence window of the hypervariable, noncoding regions between the matrix (M) and fusion (F) genes (MF-NCR) was introduced to clarify the transmission chain. From the chronological sequence analysis of MeVs with N-450 and MF-NCR sequence windows, no endemic MeV variants lasted over 4 weeks, providing strong evidence to support the contention that Taiwan has reached the status for measles elimination. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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9 pages, 3321 KiB

Open AccessArticle

RNA Interference Approach Is a Good Strategy against SARS-CoV-2

by Ying-Ray Lee, Huey-Pin Tsai, Chun-Sheng Yeh, Chiung-Yao Fang, Michael W. Y. Chan, Tzu-Yun Wu and Cheng-Huang Shen

Viruses 2023, 15(1), 100; https://doi.org/10.3390/v15010100 - 29 Dec 2022

Cited by 3 | Viewed by 1637

Abstract

COVID-19, caused by SARS-CoV-2, created a devastating outbreak worldwide and consequently became a global health concern. However, no verifiable, specifically targeted treatment has been devised for COVID-19. Several emerging vaccines have been used, but protection has not been satisfactory. The complex genetic composition [...] Read more.

COVID-19, caused by SARS-CoV-2, created a devastating outbreak worldwide and consequently became a global health concern. However, no verifiable, specifically targeted treatment has been devised for COVID-19. Several emerging vaccines have been used, but protection has not been satisfactory. The complex genetic composition and high mutation frequency of SARS-CoV-2 have caused an uncertain vaccine response. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control various infectious diseases employing post-transcriptional gene silencing through the silencing of target complementary mRNA. Here, we designed two highly effective shRNAs targeting the conserved region of RNA-dependent RNA polymerase (RdRP) and spike proteins capable of significant SARS-CoV-2 replication suppression. The efficacy of this approach suggested that the rapid development of an shRNA-based therapeutic strategy might prove to be highly effective in treating COVID-19. However, it needs further clinical trials. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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15 pages, 1922 KiB

Open AccessArticle

Rose Virome Analysis and Identification of a Novel Ilarvirus in Taiwan

by Tsung-Chi Chen, Yu-Chieh Lin, Chian-Chi Lin, Yi-Xian Lin and Yuh-Kun Chen

Viruses 2022, 14(11), 2537; https://doi.org/10.3390/v14112537 - 16 Nov 2022

Cited by 2 | Viewed by 2572

Abstract

Rose (Rosa spp.), especially R. hybrida, is one of the most popular ornamental plants in the world and the third largest cut flower crop in Taiwan. Rose mosaic disease (RMD), showing mosaic, line patterns and ringspots on leaves, is a common [...] Read more.

Rose (Rosa spp.), especially R. hybrida, is one of the most popular ornamental plants in the world and the third largest cut flower crop in Taiwan. Rose mosaic disease (RMD), showing mosaic, line patterns and ringspots on leaves, is a common rose disease caused by the complex infection of various viruses. Due to pests and diseases, the rose planting area in Taiwan has been decreasing since 2008; however, no rose virus disease has been reported in the past five decades. In the spring of 2020, rose samples showing RMD-like symptoms were observed at an organic farm in Chiayi, central Taiwan. The virome in the farm was analyzed by RNA-seq. Rose genomic sequences were filtered from the obtained reads. The remaining reads were de novo assembled to generate 294 contigs, 50 of which were annotated as viral sequences corresponding to 10 viruses. Through reverse transcription-polymerase chain reaction validation, a total of seven viruses were detected, including six known rose viruses, namely apple mosaic virus, prunus necrotic ringspot virus, rose partitivirus, apple stem grooving virus, rose spring dwarf-associated virus and rose cryptic virus 1, and a novel ilarvirus. After completing the whole genome sequencing and sequence analysis, the unknown ilarvirus was demonstrated as a putative new species, tentatively named rose ilarvirus 2. This is the first report of the rose virus disease in Taiwan. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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13 pages, 1433 KiB

Open AccessArticle

Validation of Viral Inactivation Protocols for Therapeutic Blood Products against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

by Wendimi Fatimata Belem, Ching-Hsuan Liu, Yee-Tung Hu, Thierry Burnouf and Liang-Tzung Lin

Viruses 2022, 14(11), 2419; https://doi.org/10.3390/v14112419 - 31 Oct 2022

Cited by 1 | Viewed by 1947

Abstract

Therapeutic blood products including convalescent plasma/serum and immunoglobulins concentrated from convalescent plasma, such as intravenous immunoglobulins or hyperimmune globulins, and monoclonal antibodies are passive immunotherapy options for novel coronavirus disease 2019 (COVID-19). They have been shown to improve the clinical status and biological [...] Read more.

Therapeutic blood products including convalescent plasma/serum and immunoglobulins concentrated from convalescent plasma, such as intravenous immunoglobulins or hyperimmune globulins, and monoclonal antibodies are passive immunotherapy options for novel coronavirus disease 2019 (COVID-19). They have been shown to improve the clinical status and biological and radiological parameters in some groups of COVID-19 patients. However, blood products are still potential sources of virus transmission in recipients. The use of pathogen reduction technology (PRT) should increase the safety of the products. The purpose of this study was to determine the impact of solvent/detergents (S/D) procedures on SARS-CoV-2 infectivity elimination in the plasma of donors but also on COVID-19 convalescent serum (CCS) capacity to neutralize SARS-CoV-2 infectivity. In this investigation, S/D treatment for all experiments was performed at a shortened process time (30 min). We first evaluated the impact of S/D treatments (1% TnBP/1% TritonX-45 and 1% TnBP/1% TritonX-100) on the inactivation of SARS-CoV-2 pseudoparticles (SARS-CoV-2pp)-spiked human plasma followed by S/D agent removal using a Sep-Pak Plus C18 cartridge. Both treatments were able to completely inactivate SARS-CoV-2pp infectivity to an undetectable level. Moreover, the neutralizing activity of CCS against SARS-CoV-2pp was preserved after S/D treatments. Our data suggested that viral inactivation methods using such S/D treatments could be useful in the implementation of viral inactivation/elimination processes of therapeutic blood products against SARS-CoV-2. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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30 pages, 1710 KiB

Open AccessArticle

Geographic Transmission and Epidemic History of HIV-1 CRF01_AE, CRF07_BC, and HCV Subtype-6w among Taiwanese Persons Who Inject Drugs

by Yen-Ju Chen, Jason C. Huang, Hung-Chin Tsai, Yu-Hui Lin, Kuo-Feng Hsu and Hsin-Fu Liu

Viruses 2022, 14(10), 2142; https://doi.org/10.3390/v14102142 - 28 Sep 2022

Viewed by 1516

Abstract

Persons who inject drugs (PWID) and their risk-related behaviors (e.g., unprotected sex and sharing needles/syringes/other injection equipment) have caused severe public health problems, especially in the rapid spread of HIV-1 and HCV. Here, we reconstructed the epidemic history of HIV-1 circulating recombinant form [...] Read more.

Persons who inject drugs (PWID) and their risk-related behaviors (e.g., unprotected sex and sharing needles/syringes/other injection equipment) have caused severe public health problems, especially in the rapid spread of HIV-1 and HCV. Here, we reconstructed the epidemic history of HIV-1 circulating recombinant form (CRF) 01_AE, CRF07_BC, and HCV subtype-6w among Taiwanese PWID. The timescales were estimated using phylogenetic and Bayesian coalescent analyses. The results revealed that CRF01_AE started to circulate in the Taiwanese PWID population in central Taiwan at 1992.5 (95% credible region: 1988.8–1995.9) and spread to other regions of Taiwan, while CRF07_BC was first identified in southern Taiwan at 2000.0 (95% CR: 1997.8–2002.2) and then spread northward to central-northern Taiwan. All HCV-6 strains were from Asia (that is, China, Myanmar, Taiwan, and Vietnam) and originated in 1928.1 (95% CR: 1890.2–1966.0). Furthermore, subtype-6w isolates from different regions of Taiwan appeared to share a common source that existed in the mid-1990s (95% CR: 1985.0–2001.8) or thereabouts. The routes of drug trafficking and the resulting high prevalence of HIV-1/HCV co-infections among PWID might have contributed to the virus transmission and promoted its spread worldwide. Long-term monitoring and policy implementation in at-risk populations would be useful for disease control. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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12 pages, 4267 KiB

Open AccessArticle

Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform

by Min-Yuan Chia, Chun-Yang Lin, Po-Ling Chen, Chia-Chun Lai, Tsai-Chuan Weng, Wang-Chou Sung, Alan Yung-Chih Hu and Min-Shi Lee

Viruses 2022, 14(9), 1937; https://doi.org/10.3390/v14091937 - 31 Aug 2022

Cited by 1 | Viewed by 2020

Abstract

Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and [...] Read more.

Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during influenza epidemics and pandemics. Egg-based platforms for the production of influenza vaccines are labor-intensive and unable to meet the surging demand during pandemics. Therefore, cell culture-based technology is becoming the alternative strategy for producing influenza vaccines. The current influenza H7N9 vaccine virus (NIBRG-268), a reassortant virus from A/Anhui/1/2013 (H7N9) and egg-adapted A/PR/8/34 (H1N1) viruses, could grow efficiently in embryonated eggs but not mammalian cells. Moreover, a freezing-dry formulation of influenza H7N9 vaccines with long-term stability will be desirable for pandemic preparedness, as the occurrence of influenza H7N9 pandemics is not predictable. In this study, we adapted a serum-free anchorage-independent suspension Madin-Darby Canine Kidney (MDCK) cell line for producing influenza H7N9 vaccines and compared the biochemical characteristics and immunogenicity of three influenza H7N9 vaccine antigens produced using the suspension MDCK cell-based platform without freeze-drying (S-WO-H7N9), the suspension MDCK cell-based platform with freeze-drying (S-W-H7N9) or the egg-based platform with freeze-drying (E-W-H7N9). We demonstrated these three vaccine antigens have comparable biochemical characteristics. In addition, these three vaccine antigens induced robust and comparable neutralizing antibody (NT; geometric mean between 1016 and 4064) and hemagglutinin-inhibition antibody (HI; geometric mean between 640 and 1613) titers in mice. In conclusion, the serum-free suspension MDCK cell-derived freeze-dried influenza H7N9 vaccine is highly immunogenic in mice, and clinical development is warranted. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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12 pages, 1867 KiB

Open AccessArticle

Roles of Ambient Temperature and PM_2.5 on Childhood Acute Bronchitis and Bronchiolitis from Viral Infection

by Pei-Chun Chen, Chih-Hsin Mou, Chao W. Chen, Dennis P. H. Hsieh, Shan P. Tsai, Chang-Ching Wei and Fung-Chang Sung

Viruses 2022, 14(9), 1932; https://doi.org/10.3390/v14091932 - 30 Aug 2022

Cited by 7 | Viewed by 1886

Abstract

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006–2016. [...] Read more.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006–2016. The monthly average incident CABs increased with increasing PM_2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June–August). The highest incidence was 698 cases/day at <20 °C with PM_2.5 > 37.0 μg/m³, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97–1.04) compared to 568 cases/day at <20 °C with PM_2.5 < 15.0 μg/m³ (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85–1.06) with PM_2.5 > 37.0 μg/m³ and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58–0.65) when PM_2.5 was <15.0 μg/m³. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM_2.5 concentrations, and the high PM_2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM_2.5 and CABs. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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22 pages, 5690 KiB

Open AccessArticle

Enteroviral 2B Interacts with VDAC3 to Regulate Reactive Oxygen Species Generation That Is Essential to Viral Replication

by Mei-Ling Cheng, Chien-Hsiang Wu, Kun-Yi Chien, Chien-Hsueh Lai, Guan-Jie Li, Yuan-Yu Liu, Gigin Lin and Hung-Yao Ho

Viruses 2022, 14(8), 1717; https://doi.org/10.3390/v14081717 - 04 Aug 2022

Cited by 8 | Viewed by 2288

Abstract

Enterovirus (EV) 71 caused episodes of outbreaks in China and Southeast Asia during the last few decades. We have previously reported that EV71 induces reactive oxygen species (ROS). However, the underlying mechanism remains elusive. Co-immunoprecipitation-proteomic analysis revealed that enteroviral 2B protein interacted with [...] Read more.

Enterovirus (EV) 71 caused episodes of outbreaks in China and Southeast Asia during the last few decades. We have previously reported that EV71 induces reactive oxygen species (ROS). However, the underlying mechanism remains elusive. Co-immunoprecipitation-proteomic analysis revealed that enteroviral 2B protein interacted with mitochondrial voltage-dependent anion channel 3 (VDAC3). Knockdown (KD) of VDAC3 expression specifically inhibited enteroviral replication. Single-round viral replication was also inhibited in KD cells, suggesting that VDAC3 plays an essential role in replication. Consistent with this, VDAC3 gene KD significantly reduced the EV71-induced mitochondrial ROS generation. Exogenous 2B expression could induce the mitochondrial ROS generation that was significantly reduced in VDAC3-KD cells or in the Mito-TEMPO-treated cells. Moreover, VDAC3 appears to be necessary for regulation of antioxidant metabolism. VDAC3 gene KD led to the enhancement of such pathways as hypotaurine/taurine synthesis in the infected cells. Taken together, these findings suggest that 2B and VDAC3 interact to enhance mitochondrial ROS generation, which promotes viral replication. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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19 pages, 5420 KiB

Open AccessArticle

A Reverse Mutation E143K within the PrM Protein of Zika Virus Asian Lineage Natal RGN Strain Increases Infectivity and Cytopathicity

by Chen-Sheng Lin, Wei-Jing Li, Chih-Yi Liao, Ju-Ying Kan, Szu-Hao Kung, Su-Hua Huang, Hsueh-Chou Lai and Cheng-Wen Lin

Viruses 2022, 14(7), 1572; https://doi.org/10.3390/v14071572 - 20 Jul 2022

Cited by 3 | Viewed by 1795

Abstract

Zika virus (ZIKV) is a positive-sense single-stranded RNA virus in the Flaviviridae, which is classified into two different lineages Asian and African. The outbreak of ZIKV Asian lineage isolates in 2015–2016 is associated with the increase in cases with prenatal microcephaly and Guillain–Barré [...] Read more.

Zika virus (ZIKV) is a positive-sense single-stranded RNA virus in the Flaviviridae, which is classified into two different lineages Asian and African. The outbreak of ZIKV Asian lineage isolates in 2015–2016 is associated with the increase in cases with prenatal microcephaly and Guillain–Barré syndrome, and has sparked attention throughout the world. Genome sequence alignment and the analysis of Asian and African lineage isolates indicate that amino acid changes, particular in positively charged amino acid substitutions in the pr region of prM protein might involve a phenotypic change that links with the global outbreak of ZIKV Asian-lineage. The study generated and characterized the virological properties of wild type and mutants of single-round infectious particles (SRIPs) and infectious clones (i.c.s) of ZIKV Asian-lineage Natal RGN strain, and then identified the function of amino acid substitutions at the positions 139 [Asn139→Ser139 (N139S)] and 143 [Glu143→Lys143 (E143K)] in ZIKV polyproteins (located within the pr region of prM protein) in the infectivity and cytopathogenicity. The E143K SRIP and i.c. of Natal RGN strain exhibited relatively higher levels of cytopathic effect, EGFP reporter, viral RNA and protein synthesis, and virus yield in three types of human cell lines, TE617, SF268 and HMC3, compared to wild type (WT), N139S SRIPs and i.c.s, which displayed more efficiency in replication kinetics. Additionally, E143K Natal RGN i.c. had greater activities of virus attachment and entry, yielded higher titers of intracellular and extracellular virions, and assembled the E proteins near to the plasma membrane in infected cells than the other i.c.s. The results indicate that the positively charged amino acid residue Lys143, a conserved residue in the pr region of prM of ZIKV African lineages, plays a crucial role in viral replication kinetics, including viral attachment, entry, assembly and egress. Thus, the negatively charged amino acid residue Glu143 within the pr region of prM leads to an alteration of the phenotypes, in particular, a lower replication efficiency of ZIKV Asian-lineage isolates with the attenuation of infectivity and cytopathicity. Full article

(This article belongs to the Special Issue Virology Research in Taiwan)

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