scholarly journals Cooperative nature of viral replication

2020 ◽  
Vol 6 (49) ◽  
pp. eabd4942
Author(s):  
Iván Andreu-Moreno ◽  
Juan-Vicente Bou ◽  
Rafael Sanjuán
Keyword(s):  
Viral Replication ◽  
Viral Fitness ◽  
Progeny Production ◽  
Short Term ◽  
Viral Particles ◽  
Viral Progeny ◽  
Cooperative Process ◽  
Complex Models ◽  
Rapid Dissemination ◽  
Human Viruses

The ability of viruses to infect their hosts depends on rapid dissemination following transmission. The notion that viral particles function as independent propagules has been challenged by recent observations suggesting that viral aggregates show enhanced infectivity and faster spread. However, these observations remain poorly understood. Here, we show that viral replication is a cooperative process, such that entry of multiple viral genome copies into the same cell disproportionately increases short-term viral progeny production. This cooperativity arises from the positive feedback established between replication templates and virus-encoded products involved in replication and should be a general feature of viruses. We develop a simple model that captures this effect, verify that cooperativity also emerges in more complex models for specific human viruses, validate our predictions experimentally using different mammalian viruses, and discuss the implications of cooperative replication for viral fitness.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

scholarly journals Exploring Author Profiling for Fake News Detection

2021 ◽  
Author(s):  
Shloak Rathod
Keyword(s):  
False Positive Rate ◽  
True Positive Rate ◽  
Supervised Machine Learning ◽  
Online Media ◽  
Fake News ◽  
Writing Style ◽  
Short Term ◽  
Positive Rate ◽  
Rapid Dissemination ◽  
Author Profiling

<div><div><div><p>The proliferation of online media allows for the rapid dissemination of unmoderated news, unfortunately including fake news. The extensive spread of fake news poses a potent threat to both individuals and society. This paper focuses on designing author profiles to detect authors who are primarily engaged in publishing fake news articles. We build on the hypothesis that authors who write fake news repeatedly write only fake news articles, at least in short-term periods. Fake news authors have a distinct writing style compared to real news authors, who naturally want to maintain trustworthiness. We explore the potential to detect fake news authors by designing authors’ profiles based on writing style, sentiment, and co-authorship patterns. We evaluate our approach using a publicly available dataset with over 5000 authors and 20000 articles. For our evaluation, we build and compare different classes of supervised machine learning models. We find that the K-NN model performed the best, and it could detect authors who are prone to writing fake news with an 83% true positive rate with only a 5% false positive rate.</p></div></div></div>

scholarly journals Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Concepción Casado ◽  
Sara Marrero-Hernández ◽  
Daniel Márquez-Arce ◽  
María Pernas ◽  
Sílvia Marfil ◽  
...  
Keyword(s):  
Viral Replication ◽  
Clinical Phenotype ◽  
Functional Characterization ◽  
Viral Fitness ◽  
Elite Controller ◽  
Replication Capacity ◽  
Viral Fusion ◽  
Elite Controllers ◽  
Hiv 1

ABSTRACTA small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of host, immune, and viral factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting the contribution of common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env) glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection, being a key factor of viral fitnessin vitro, cytopathicity, and infection progressionin vivo. Therefore, we isolated full-lengthenvgenes from viruses of these patients and from chronically infected control individuals. Functional characterization of the initial events of the viral infection showed that Envs from the LTNP-ECs were ineffective in the binding to CD4 and in the key triggering of actin/tubulin-cytoskeleton modifications compared to Envs from chronic patients. The viral properties of the cluster viruses result in a defective viral fusion, entry, and infection, and these properties were inherited by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and signaling defects may contribute to the low viral replication capacity and transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC phenotype of these individuals. These results highlight the important role of viral characteristics in the LTNP-EC clinical phenotype. These Env viral properties were common to all the cluster viruses and thus support the heritability of the viral characteristics.IMPORTANCEHIV-1 long-term nonprogressor elite controller patients, due to their permanent control of viral replication, have been the object of numerous studies to identify the factors responsible for this clinical phenotype. In this work, we analyzed the viral characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP-EC patients. These envelopes showed ineffective binding to CD4 and the subsequent signaling activity to modify actin/tubulin cytoskeletons, which result in low fusion and deficient entry and infection capacities. These Env viral characteristics could explain the nonprogressor clinical phenotype of these patients. In addition, these inefficientenvviral properties were present in all viruses of the cluster, supporting the heritability of the viral phenotype.

scholarly journals HLA-B57/B*5801 Human Immunodeficiency Virus Type 1 Elite Controllers Select for Rare Gag Variants Associated with Reduced Viral Replication Capacity and Strong Cytotoxic T-Lymphotye Recognition

2008 ◽  
Vol 83 (6) ◽  
pp. 2743-2755 ◽  
Author(s):  
Toshiyuki Miura ◽  
Mark A. Brockman ◽  
Arne Schneidewind ◽  
Michael Lobritz ◽  
Florencia Pereyra ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Fitness ◽  
Replication Capacity ◽  
Elite Controllers ◽  
Immunodeficiency Virus ◽  
Viral Replication Capacity

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) elite controllers (EC) maintain viremia below the limit of commercial assay detection (<50 RNA copies/ml) in the absence of antiviral therapy, but the mechanisms of control remain unclear. HLA-B57 and the closely related allele B*5801 are particularly associated with enhanced control and recognize the same Gag240-249 TW10 epitope. The typical escape mutation (T242N) within this epitope diminishes viral replication capacity in chronically infected persons; however, little is known about TW10 epitope sequences in residual replicating viruses in B57/B*5801 EC and the extent to which mutations within this epitope may influence steady-state viremia. Here we analyzed TW10 in a total of 50 B57/B*5801-positive subjects (23 EC and 27 viremic subjects). Autologous plasma viral sequences from both EC and viremic subjects frequently harbored the typical cytotoxic T-lymphocyte (CTL)-selected mutation T242N (15/23 sequences [65.2%] versus 23/27 sequences [85.1%], respectively; P = 0.18). However, other unique mutants were identified in HIV controllers, both within and flanking TW10, that were associated with an even greater reduction in viral replication capacity in vitro. In addition, strong CTL responses to many of these unique TW10 variants were detected by gamma interferon-specific enzyme-linked immunospot assay. These data suggest a dual mechanism for durable control of HIV replication, consisting of viral fitness loss resulting from CTL escape mutations together with strong CD8 T-cell immune responses to the arising variant epitopes.

scholarly journals Survivin Overexpression Has a Negative Effect on Feline Calicivirus Infection

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 996
Author(s):  
Oscar Salvador Barrera-Vázquez ◽  
Clotilde Cancio-Lonches ◽  
Carlos Emilio Miguel-Rodríguez ◽  
Monica Margarita Valdes Pérez ◽  
Ana Lorena Gutiérrez-Escolano
Keyword(s):  
Virus Production ◽  
Feline Calicivirus ◽  
Protective Effects ◽  
Murine Norovirus ◽  
Progeny Production ◽  
Apoptotic Protein ◽  
Viral Yield ◽  
Viral Progeny ◽  
Negative Effect ◽  
Replicative Cycle

It is known that levels of the anti-apoptotic protein survivin are reduced during Murine norovirus MNV-1 and Feline calicivirus (FCV) infection as part of the apoptosis establishment required for virus release and propagation in the host. Recently, our group has reported that overexpression of survivin causes a reduction of FCV protein synthesis and viral progeny production, suggesting that survivin may affect early steps of the replicative cycle. Using immunofluorescence assays, we observed that overexpression of survivin, resulted in the reduction of FCV infection not only in transfected but also in the neighboring nontransfected CrFK cells, thus suggesting autocrine and paracrine protective effects. Cells treated with the supernatants collected from CrFK cells overexpressing survivin showed a reduction in FCV but not MNV-1 protein production and viral yield, suggesting that FCV binding and/or entry were specifically altered. The reduced ability of FCV to bind to the surface of the cells overexpressing survivin, or treated with the supernatants collected from these cells, correlate with the reduction in the cell surface of the FCV receptor, the feline junctional adhesion molecule (fJAM) 1, while no effect was observed in the cells transfected with the pAm-Cyan vector or in cells treated with the corresponding supernatants. Moreover, the overexpression of survivin affects neither Vaccinia virus (VACV) production in CrFK cells nor MNV-1 virus production in RAW 267.4 cells, indicating that the effect is specific for FCV. All of these results taken together indicate that cells that overexpress survivin, or cell treatment with the conditioned medium from these cells, results in the reduction of the fJAM-1 molecule and, therefore, a specific reduction in FCV entry and infection.

scholarly journals Impact of Primary Elvitegravir Resistance-Associated Mutations in HIV-1 Integrase on Drug Susceptibility and Viral Replication Fitness

2013 ◽  
Vol 57 (6) ◽  
pp. 2654-2663 ◽  
Author(s):  
Michael E. Abram ◽  
Rebecca M. Hluhanich ◽  
Derrick D. Goodman ◽  
Kristen N. Andreatta ◽  
Nicolas A. Margot ◽  
...  
Keyword(s):  
Viral Replication ◽  
Drug Susceptibility ◽  
Viral Fitness ◽  
Cross Resistance ◽  
Replication Capacity ◽  
Strand Transfer ◽  
Recombinant Viruses ◽  
Transfer Inhibitor ◽  
Replication Fitness ◽  
Hiv 1

ABSTRACTElvitegravir (EVG) is an effective HIV-1 integrase (IN) strand transfer inhibitor (INSTI) in advanced clinical development. Primary INSTI resistance-associated mutations (RAMs) at six IN positions have been identified in HIV-1-infected patients failing EVG-containing regimens in clinical studies: T66I/A/K, E92Q/G, T97A, S147G, Q148R/H/K, and N155H. In this study, the effect of these primary IN mutations, alone and in combination, on susceptibility to the INSTIs EVG, raltegravir (RAL), and dolutegravir (DTG); IN enzyme activities; and viral replication fitness was characterized. Recombinant viruses containing the six most common mutations exhibited a range of reduced EVG susceptibility: 92-fold for Q148R, 30-fold for N155H, 26-fold for E92Q, 10-fold for T66I, 4-fold for S147G, and 2-fold for T97A. Less commonly observed primary IN mutations also showed a range of reduced EVG susceptibilities: 40- to 94-fold for T66K and Q148K and 5- to 10-fold for T66A, E92G, and Q148H. Some primary IN mutations exhibited broad cross-resistance between EVG and RAL (T66K, E92Q, Q148R/H/K, and N155H), while others retained susceptibility to RAL (T66I/A, E92G, T97A, and S147G). Dual combinations of primary IN mutations further reduced INSTI susceptibility, replication capacity, and viral fitness relative to either mutation alone. Susceptibility to DTG was retained by single primary IN mutations but reduced by dual mutation combinations with Q148R. Primary EVG RAMs also diminished IN enzymatic activities, concordant with their structural proximity to the active site. Greater reductions in viral fitness of dual mutation combinations may explain why some primary INSTI RAMs do not readily coexist on the same HIV-1 genome but rather establish independent pathways of resistance to EVG.

scholarly journals Preventing co-infection: a viral strategy with short-term benefits and long-term drawbacks

2021 ◽  
Author(s):  
Michael Hunter ◽  
Diana Fusco
Keyword(s):  
Growth Rate ◽  
Life History ◽  
Negative Impact ◽  
Viral Evolution ◽  
Viral Fitness ◽  
Viral Population ◽  
Short Term ◽  
Life History Parameters ◽  
Wide Range

ABSTRACTViral co-infection occurs when multiple distinct viral particles infect the same host. This can impact viral evolution through intracellular interactions, complementation, reassortment and recombination. In nature many viral species are found to have a wide range of mechanisms to prevent co-infection, which raises the question of how viral evolution is impacted by this strategic choice. Here, we address this question in a model viral system, the ubiquitous bacteriophage and its host bacteria. Using a stochastic model of phage-host interactions in agent-based simulations, we first characterise the behaviour of neutral mutants and find that co-infection decreases the strength of genetic drift. We then quantify how variations in the phage life history parameters affect viral fitness. Importantly, we find that the growth rate (dis)advantage associated with variations in life history parameters can be dramatically different from the competitive (dis)advantage measured in direct-competition simulations. Additionally, we find that co-infection facilitates the fixation of beneficial mutations and the removal of deleterious ones, suggesting that selection is more efficient in co-infecting populations. We also observe, however, that in populations which allow co-infection, a mutant that prevents it displays a substantial competitive advantage over the rest of the population, and will eventually fix even if it displays a much lower growth rate in isolation. Our findings suggest that while preventing co-infection can have a negative impact on the long-term evolution of a viral population, in the short-term it is ultimately a winning strategy, possibly explaining the prevalence of phage capable of preventing co-infection in nature.

scholarly journals A quantitative approach to assess influenza A virus fitness and transmission in guinea pigs

2021 ◽  
Author(s):  
Shamika Danzy ◽  
Anice C. Lowen ◽  
John Steel
Keyword(s):  
Viral Load ◽  
Viral Replication ◽  
Human Population ◽  
Influenza A ◽  
Transmission Efficiency ◽  
Viral Fitness ◽  
Influenza Pandemics ◽  
Peak Viral Load ◽  
Key Driver ◽  
Kinetics Of

Efforts to estimate the risk posed by potentially pandemic influenza A viruses (IAV), and to understand the mechanisms governing interspecies transmission, have been hampered by a lack of animal models that yield relevant and statistically robust measures of viral fitness. To address this gap, we monitored several quantitative measures of fitness in a guinea pig model: infectivity, magnitude of replication, kinetics of replication, efficiency of transmission, and kinetics of transmission. With the goal of identifying metrics that distinguish human- and non-human-adapted IAV we compared strains derived from humans to those circulating in swine and canine populations. Influenza A/Panama/2007/99 (H3N2), A/Netherlands/602/2009 (H1N1), A/swine/Kansas/77778/2007 (H1N1), A/swine/Spain/53207/2004 [M1 P41A] (H1N1), and A/canine/Illinois/41915/2015 (H3N2) viruses were evaluated. Our results revealed higher infectivity and faster kinetics of viral replication and transmission for human and canine strains compared to the swine viruses. Conversely, peak viral titers and efficiency of transmission were higher for human strains relative to both swine and canine IAVs. Total viral loads were comparable among all strains tested. When analyzed together, data from all strains point to peak viral load as a key driver of transmission efficiency and replication kinetics as a key driver of transmission kinetics. While the dose initiating infection did not strongly impact peak viral load, dose was found to modulate kinetics of viral replication and, in turn, timing of transmission. Taken together, our results point to peak viral load and transmission efficiency as key metrics differentiating human and non-human IAVs and suggest that high peak viral load precipitates robust transmission. Importance Influenza pandemics occur when an IAV from non-human hosts enters the human population and adapts to give rise to a lineage capable of sustained transmission among humans. Despite recurring zoonotic infections involving avian or swine adapted IAVs, influenza pandemics occur infrequently because IAVs typically exhibit low fitness in a new host species. Anticipating when a zoonosis might lead to a pandemic is both critical for public health preparedness and extremely challenging. The approach to characterizing IAVs reported here is designed to aid risk assessment efforts by generating rigorous and quantitative data on viral phenotypes relevant for emergence. Our data suggest that the ability to replicate to high titers and transmit efficiently irrespective of initial dose are key characteristics distinguishing IAVs that have established sustained circulation in the human population from IAVs that circulate in non-human mammalian hosts.

scholarly journals Repurposing inhibitors for SARS-CoV2 main protease

2020 ◽  
Author(s):  
Kumar Sharp
Keyword(s):  
Viral Replication ◽  
Active Sites ◽  
Drug Repurposing ◽  
Chemotherapeutic Drugs ◽  
Short Term ◽  
Main Protease ◽  
Potential Binding ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract SARS-CoV2 main protease is important for viral replication and one of the most potential targets for drug development in this current pandemic. Drug repurposing is a promising field to provide potential short-term acceptable therapy for management of coronavirus till a specific anti-viral for coronavirus is developed. In-silico drug repurposing screening is the current fastest way to repurpose drugs by targeting active sites in fraction of seconds. In this study, SARS-CoV2 main protease is being targeted by 1050 FDA-approved drugs to inhibit its activity thereby interfering with viral replication. Chemotherapeutic drugs and anti-retroviral drugs have shown potential binding as inhibitor. In-vitro and clinical trials required to establish final fact.

scholarly journals Characterization of Adenovirus 5 E1A Exon 1 Deletion Mutants in the Viral Replicative Cycle

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 213
Author(s):  
Rita Costa ◽  
Nikolas Akkerman ◽  
Drayson Graves ◽  
Leandro Crisostomo ◽  
Scott Bachus ◽  
...  
Keyword(s):  
Viral Replication ◽  
Virus Replication ◽  
Cellular Localization ◽  
Negative Impact ◽  
S Phase ◽  
Viral Fitness ◽  
Deletion Mutants ◽  
Gene And Protein Expression ◽  
Exon 1 ◽  
Replicative Cycle

Human adenovirus infection is driven by Early region 1A (E1A) proteins, which are the first proteins expressed following the delivery of the viral genome to the cellular nucleus. E1A is responsible for reprogramming the infected cell to support virus replication alongside the activation of expression of all viral transcriptional units during the course of the infection. Although E1A has been extensively studied, most of these studies have focused on understanding the conserved region functions outside of a full infection. Here, we investigated the effects of small deletions in E1A exon 1 on the viral replicative cycle. Almost all deletions were found to have a negative impact on viral replication with the exception of one deletion found in the mutant dl1106, which replicated better than the wild-type E1A expressing dl309. In addition to growth, we assessed the virus mutants for genome replication, induction of the cytopathic effect, gene and protein expression, sub-cellular localization of E1A mutant proteins, induction of cellular S-phase, and activation of S-phase specific cellular genes. Importantly, our study found that virus replication is likely limited by host-specific factors, rather than specific viral aspects such as the ability to replicate genomes or express late proteins, after a certain level of these has been expressed. Furthermore, we show that mutants outside of the conserved regions have significant influence on viral fitness. Overall, our study is the first comprehensive evaluation of the dl1100 series of exon 1 E1A deletion mutants in viral fitness and provides important insights into the contribution that E1A makes to viral replication in normal human cells.

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