Emerging RNA Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 46064

Special Issue Editors

1. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
2. Internal Medicine Mildred H Vacek and John R Vacek Distinguished Chair in Honor of President Truman G. Blocker, Jr., University of Texas Medical Branch, Galveston, TX 77555, USA
3. Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore
Interests: RNA biology; RNA virology
Saw Swee Hock School of Public Health and Department of Pharmacy, National University of Singapore, Singapore 119077, Singapore
Interests: RNA virology; mechanisms of pathogenesis
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore
Interests: dengue virology and pathogenesis; flavivirus-host interactions; development of molecular correlates of vaccine and antiviral safety and efficacy

Special Issue Information

Dear Colleagues,

Pathogenic RNA viruses represent an unmatched threat to global health. Salient examples from the past and present are the influenza pandemic that started in 1918, the re-emergence of dengue in the 20th century, the AIDS pandemic, the SARS outbreak of 2003, the Ebola virus outbreak of 2013, the Zika virus pandemic of 2016, and COVID-19. The later, caused by the betacoronavirus SARS-CoV-2, has made it evident that despite great advances in science and health, the world is not prepared to effectively deal with a highly infectious and pathogenic virus. This may not be surprising since we do not know what we do not know—i.e., it is not possible to specifically predict what the next pandemic threat will be and study it ahead of time. Nonetheless, we frame this volume around the idea that we should create “knowledge neighborhoods” that will enable a more expeditious and effective response to an emergent pathogen. Our bias is that a deep understanding of the molecular details of the neighborhood—which in one instance could be defined as coronaviruses—can lead to the discovery of general vulnerabilities—e.g., antivirals targeting all coronaviruses. Since we base this volume on molecular positivism, we also include contributions that offer cautionary and dissenting viewpoints.

Prof. Dr. Mariano Agustin Garcia-Blanco
Dr. October Sessions
Professor Eng Eong Ooi
Guest Editor

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Keywords

  • RNA viruses
  • RNA
  • emerging viruses
  • zoonosis

Published Papers (11 papers)

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Research

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14 pages, 2694 KiB  
Article
Serological Evidence of Widespread Zika Transmission across the Philippines
by Joseph R. Biggs, Ava Kristy Sy, Oliver J. Brady, Adam J. Kucharski, Sebastian Funk, Yun-Hung Tu, Mary Anne Joy Reyes, Mary Ann Quinones, William Jones-Warner, James Ashall, Ferchito L. Avelino, Nemia L. Sucaldito, Amado O. Tandoc, Eva Cutiongco-de la Paz, Maria Rosario Z. Capeding, Carmencita D. Padilla, Martin L. Hibberd and Julius Clemence R. Hafalla
Viruses 2021, 13(8), 1441; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081441 - 23 Jul 2021
Cited by 4 | Viewed by 3946
Abstract
Zika virus (ZIKV) exposure across flavivirus-endemic countries, including the Philippines, remains largely unknown despite sporadic case reporting and environmental suitability for transmission. Using laboratory surveillance data from 2016, 997 serum samples were randomly selected from suspected dengue (DENV) case reports across the Philippines [...] Read more.
Zika virus (ZIKV) exposure across flavivirus-endemic countries, including the Philippines, remains largely unknown despite sporadic case reporting and environmental suitability for transmission. Using laboratory surveillance data from 2016, 997 serum samples were randomly selected from suspected dengue (DENV) case reports across the Philippines and assayed for serological markers of short-term (IgM) and long-term (IgG) ZIKV exposure. Using mixture models, we re-evaluated ZIKV IgM/G seroprevalence thresholds and used catalytic models to quantify the force of infection (attack rate, AR) from age-accumulated ZIKV exposure. While we observed extensive ZIKV/DENV IgG cross-reactivity, not all individuals with active DENV presented with elevated ZIKV IgG, and a proportion of dengue-negative cases (DENV IgG-) were ZIKV IgG-positive (14.3%, 9/63). We identified evidence of long-term, yet not short-term, ZIKV exposure across Philippine regions (ZIKV IgG+: 31.5%, 314/997) which was geographically uncorrelated with DENV exposure. In contrast to the DENV AR (12.7% (95%CI: 9.1–17.4%)), the ZIKV AR was lower (5.7% (95%CI: 3–11%)) across the country. Our results provide evidence of widespread ZIKV exposure across the Philippines and suggest the need for studies to identify ZIKV infection risk factors over time to better prepare for potential future outbreaks. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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20 pages, 16979 KiB  
Article
Development and Characterization of a cDNA-Launch Recombinant Simian Hemorrhagic Fever Virus Expressing Enhanced Green Fluorescent Protein: ORF 2b’ Is Not Required for In Vitro Virus Replication
by Yingyun Cai, Shuiqing Yu, Ying Fang, Laura Bollinger, Yanhua Li, Michael Lauck, Elena N. Postnikova, Steven Mazur, Reed F. Johnson, Courtney L. Finch, Sheli R. Radoshitzky, Gustavo Palacios, Thomas C. Friedrich, Tony L. Goldberg, David H. O’Connor, Peter B. Jahrling and Jens H. Kuhn
Viruses 2021, 13(4), 632; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040632 - 07 Apr 2021
Cited by 5 | Viewed by 2702
Abstract
Simian hemorrhagic fever virus (SHFV) causes acute, lethal disease in macaques. We developed a single-plasmid cDNA-launch infectious clone of SHFV (rSHFV) and modified the clone to rescue an enhanced green fluorescent protein-expressing rSHFV-eGFP that can be used for rapid and quantitative detection of [...] Read more.
Simian hemorrhagic fever virus (SHFV) causes acute, lethal disease in macaques. We developed a single-plasmid cDNA-launch infectious clone of SHFV (rSHFV) and modified the clone to rescue an enhanced green fluorescent protein-expressing rSHFV-eGFP that can be used for rapid and quantitative detection of infection. SHFV has a narrow cell tropism in vitro, with only the grivet MA-104 cell line and a few other grivet cell lines being susceptible to virion entry and permissive to infection. Using rSHFV-eGFP, we demonstrate that one cricetid rodent cell line and three ape cell lines also fully support SHFV replication, whereas 55 human cell lines, 11 bat cell lines, and three rodent cells do not. Interestingly, some human and other mammalian cell lines apparently resistant to SHFV infection are permissive after transfection with the rSHFV-eGFP cDNA-launch plasmid. To further demonstrate the investigative potential of the infectious clone system, we introduced stop codons into eight viral open reading frames (ORFs). This approach suggested that at least one ORF, ORF 2b’, is dispensable for SHFV in vitro replication. Our proof-of-principle experiments indicated that rSHFV-eGFP is a useful tool for illuminating the understudied molecular biology of SHFV. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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10 pages, 1303 KiB  
Communication
Population-Specific ACE2 Single-Nucleotide Polymorphisms Have Limited Impact on SARS-CoV-2 Infectivity In Vitro
by Mei Hashizume, Gabriel Gonzalez, Chikako Ono, Ayako Takashima and Masaharu Iwasaki
Viruses 2021, 13(1), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010067 - 06 Jan 2021
Cited by 19 | Viewed by 5003
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), employs host-cell angiotensin-converting enzyme 2 (ACE2) for cell entry. Genetic analyses of ACE2 have identified several single-nucleotide polymorphisms (SNPs) specific to different human populations. Molecular dynamics simulations have [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), employs host-cell angiotensin-converting enzyme 2 (ACE2) for cell entry. Genetic analyses of ACE2 have identified several single-nucleotide polymorphisms (SNPs) specific to different human populations. Molecular dynamics simulations have indicated that several of these SNPs could affect interactions between SARS-CoV-2 and ACE2, thereby providing a partial explanation for the regional differences observed in SARS-CoV-2 infectivity and severity. However, the significance of population-specific ACE2 SNPs in SARS-CoV-2 infectivity is unknown, as no in vitro validation studies have been performed. Here, we analyzed the impact of eight SNPs found in specific populations on receptor binding and cell entry in vitro. Except for a SNP causing a nonsense mutation that reduced ACE2 expression, none of the selected SNPs markedly altered the interaction between ACE2 and the SARS-CoV-2 spike protein (SARS-2-S), which is responsible for receptor recognition and cell entry, or the efficiency of viral cell entry mediated by SARS-2-S. Our findings indicate that ACE2 polymorphisms have limited impact on the ACE2-dependent cell entry of SARS-CoV-2 and underscore the importance of future studies on the involvement of population-specific SNPs of other host genes in susceptibility toward SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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Review

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10 pages, 465 KiB  
Review
RNA Viruses, Pandemics and Anticipatory Preparedness
by Mariano A. Garcia-Blanco, Eng Eong Ooi and October M. Sessions
Viruses 2022, 14(10), 2176; https://0-doi-org.brum.beds.ac.uk/10.3390/v14102176 - 30 Sep 2022
Cited by 3 | Viewed by 2123
Abstract
RNA viruses are likely to cause future pandemics and therefore we must create and organize a deep knowledge of these viruses to prevent and manage this risk. Assuming prevention will fail, at least once, we must be prepared to manage a future pandemic [...] Read more.
RNA viruses are likely to cause future pandemics and therefore we must create and organize a deep knowledge of these viruses to prevent and manage this risk. Assuming prevention will fail, at least once, we must be prepared to manage a future pandemic using all resources available. We emphasize the importance of having safe vaccine candidates and safe broad-spectrum antivirals ready for rapid clinical translation. Additionally, we must have similar tools to be ready for outbreaks of RNA viruses among animals and plants. Finally, similar coordination should be accomplished for other pathogens with pandemic potential. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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14 pages, 952 KiB  
Review
Computational and Experimental Approaches to Study the RNA Secondary Structures of RNA Viruses
by Siwy Ling Yang, Riccardo Delli Ponti, Yue Wan and Roland G. Huber
Viruses 2022, 14(8), 1795; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081795 - 16 Aug 2022
Viewed by 2212
Abstract
Most pandemics of recent decades can be traced to RNA viruses, including HIV, SARS, influenza, dengue, Zika, and SARS-CoV-2. These RNA viruses impose considerable social and economic burdens on our society, resulting in a high number of deaths and high treatment costs. As [...] Read more.
Most pandemics of recent decades can be traced to RNA viruses, including HIV, SARS, influenza, dengue, Zika, and SARS-CoV-2. These RNA viruses impose considerable social and economic burdens on our society, resulting in a high number of deaths and high treatment costs. As these RNA viruses utilize an RNA genome, which is important for different stages of the viral life cycle, including replication, translation, and packaging, studying how the genome folds is important to understand virus function. In this review, we summarize recent advances in computational and high-throughput RNA structure-mapping approaches and their use in understanding structures within RNA virus genomes. In particular, we focus on the genome structures of the dengue, Zika, and SARS-CoV-2 viruses due to recent significant outbreaks of these viruses around the world. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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18 pages, 1624 KiB  
Review
SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives
by Samuel Long
Viruses 2021, 13(10), 1923; https://0-doi-org.brum.beds.ac.uk/10.3390/v13101923 - 24 Sep 2021
Cited by 32 | Viewed by 5174 | Correction
Abstract
SARS-CoV-2, the etiologic agent at the root of the ongoing COVID-19 pandemic, harbors a large RNA genome from which a tiered ensemble of subgenomic RNAs (sgRNAs) is generated. Comprehensive definition and investigation of these RNA products are important for understanding SARS-CoV-2 pathogenesis. This [...] Read more.
SARS-CoV-2, the etiologic agent at the root of the ongoing COVID-19 pandemic, harbors a large RNA genome from which a tiered ensemble of subgenomic RNAs (sgRNAs) is generated. Comprehensive definition and investigation of these RNA products are important for understanding SARS-CoV-2 pathogenesis. This review summarizes the recent progress on SARS-CoV-2 sgRNA identification, characterization, and application as a viral replication marker. The significance of these findings and potential future research areas of interest are discussed. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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24 pages, 2411 KiB  
Review
Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection
by Christine E. Peters and Jan E. Carette
Viruses 2021, 13(2), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020166 - 22 Jan 2021
Cited by 8 | Viewed by 4668
Abstract
Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of [...] Read more.
Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of how non-polio enteroviruses co-opt cellular pathways has greatly increased, revealing intricate host–virus relationships. In this review, we focus on newly identified mechanisms by which enteroviruses hijack the cellular machinery to promote their replication and spread, and address their potential for the development of host-directed therapeutics. Specifically, we discuss newly identified cellular receptors and their contribution to neurotropism and spread, host factors required for viral entry and replication, and recent insights into lipid acquisition and replication organelle biogenesis. The comprehensive knowledge of common cellular pathways required by enteroviruses could expose vulnerabilities amenable for host-directed therapeutics against a broad spectrum of enteroviruses. Since this will likely include newly arising strains, it will better prepare us for future epidemics. Moreover, identifying host proteins specific to neurovirulent strains may allow us to better understand factors contributing to the neurotropism of these viruses. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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14 pages, 296 KiB  
Review
Antiviral Compounds for Blocking Arboviral Transmission in Mosquitoes
by Shengzhang Dong and George Dimopoulos
Viruses 2021, 13(1), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010108 - 14 Jan 2021
Cited by 12 | Viewed by 3707
Abstract
Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent [...] Read more.
Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
12 pages, 885 KiB  
Review
Construction of Stable Reporter Flaviviruses and Their Applications
by Coleman Baker and Pei-Yong Shi
Viruses 2020, 12(10), 1082; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101082 - 25 Sep 2020
Cited by 14 | Viewed by 2836
Abstract
Flaviviruses are significant human pathogens that cause frequent emerging and reemerging epidemics around the world. Better molecular tools for studying, diagnosing, and treating these diseases are needed. Reporter viruses represent potent tools to fill this gap but have been hindered by genetic instability. [...] Read more.
Flaviviruses are significant human pathogens that cause frequent emerging and reemerging epidemics around the world. Better molecular tools for studying, diagnosing, and treating these diseases are needed. Reporter viruses represent potent tools to fill this gap but have been hindered by genetic instability. Recent advances have overcome these hurdles, opening the way for increased use of stable reporter flaviviruses to diagnose infections, screen and study antiviral compounds, and serve as potential vaccine vectors. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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Other

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1 pages, 147 KiB  
Correction
Correction: Long, S. SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives. Viruses 2020, 13, 1923
by Samuel Long
Viruses 2022, 14(7), 1406; https://0-doi-org.brum.beds.ac.uk/10.3390/v14071406 - 28 Jun 2022
Cited by 1 | Viewed by 785
Abstract
The author is no longer affiliated with the original institution “AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA”, so the author wishes to change the affiliation to “Independent Researcher, Clarksburg, MD 20871, USA” [...] Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
20 pages, 2538 KiB  
Opinion
Mitigating Future Respiratory Virus Pandemics: New Threats and Approaches to Consider
by Gregory C. Gray, Emily R. Robie, Caleb J. Studstill and Charles L. Nunn
Viruses 2021, 13(4), 637; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040637 - 08 Apr 2021
Cited by 22 | Viewed by 10966
Abstract
Despite many recent efforts to predict and control emerging infectious disease threats to humans, we failed to anticipate the zoonotic viruses which led to pandemics in 2009 and 2020. The morbidity, mortality, and economic costs of these pandemics have been staggering. We desperately [...] Read more.
Despite many recent efforts to predict and control emerging infectious disease threats to humans, we failed to anticipate the zoonotic viruses which led to pandemics in 2009 and 2020. The morbidity, mortality, and economic costs of these pandemics have been staggering. We desperately need a more targeted, cost-efficient, and sustainable strategy to detect and mitigate future zoonotic respiratory virus threats. Evidence suggests that the transition from an animal virus to a human pathogen is incremental and requires a considerable number of spillover events and considerable time before a pandemic variant emerges. This evolutionary view argues for the refocusing of public health resources on novel respiratory virus surveillance at human–animal interfaces in geographical hotspots for emerging infectious diseases. Where human–animal interface surveillance is not possible, a secondary high-yield, cost-efficient strategy is to conduct novel respiratory virus surveillance among pneumonia patients in these same hotspots. When novel pathogens are discovered, they must be quickly assessed for their human risk and, if indicated, mitigation strategies initiated. In this review, we discuss the most common respiratory virus threats, current efforts at early emerging pathogen detection, and propose and defend new molecular pathogen discovery strategies with the goal of preempting future pandemics. Full article
(This article belongs to the Special Issue Emerging RNA Viruses)
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