scholarly journals Why viruses sometimes disperse in groups†

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Rafael Sanjuán ◽  
María-Isabel Thoulouze
Keyword(s):  
Genetic Relatedness ◽  
Lipid Vesicles ◽  
Viral Fitness ◽  
Target Cells ◽  
Spatial And Temporal Scales ◽  
Viral Genomes ◽  
Antiviral Responses ◽  
Viral Spread ◽  
Protein Matrices ◽  
Viral Components

AbstractMany organisms disperse in groups, yet this process is understudied in viruses. Recent work, however, has uncovered different types of collective infectious units, all of which lead to the joint delivery of multiple viral genome copies to target cells, favoring co-infections. Collective spread of viruses can occur through widely different mechanisms, including virion aggregation driven by specific extracellular components, cloaking inside lipid vesicles, encasement in protein matrices, or binding to cell surfaces. Cell-to-cell viral spread, which allows the transmission of individual virions in a confined environment, is yet another mode of clustered virus dissemination. Nevertheless, the selective advantages of dispersing in groups remain poorly understood in most cases. Collective dispersal might have emerged as a means of sharing efficacious viral transmission vehicles. Alternatively, increasing the cellular multiplicity of infection may confer certain short-term benefits to viruses, such as overwhelming antiviral responses, avoiding early stochastic loss of viral components required for initiating infection, or complementing genetic defects present in different viral genomes. However, increasing infection multiplicity may also entail long-term costs, such as mutation accumulation and the evolution of defective particles or other types of cheater viruses. These costs and benefits, in turn, should depend on the genetic relatedness among collective infectious unit members. Establishing the genetic basis of collective viral dispersal and performing controlled experiments to pinpoint fitness effects at different spatial and temporal scales should help us clarify the implications of these spread modes for viral fitness, pathogenicity, and evolution.

scholarly journals Collective Viral Spread Mediated by Virion Aggregates Promotes the Evolution of Defective Interfering Particles

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Iván Andreu-Moreno ◽  
Rafael Sanjuán
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Viral Infections ◽  
Cell Types ◽  
Viral Fitness ◽  
Target Cells ◽  
Short Term ◽  
Defective Interfering Particles ◽  
Viral Genomes ◽  
Viral Spread ◽  
Vesicular Stomatitis

ABSTRACT A growing number of studies report that viruses can spread in groups in so-called collective infectious units. By increasing the cellular multiplicity of infection, collective dispersal may allow for social-like interactions, such as cooperation or cheating. Yet, little is known about how such interactions evolve. In previous work with vesicular stomatitis virus, we showed that virion aggregation accelerates early infection stages in most cell types, providing a short-term fitness benefit to the virus. Here, we examine the effects of virion aggregation over several infection cycles. Flow cytometry, deep sequencing, infectivity assays, reverse transcription-quantitative PCR, and electron microscopy revealed that virion aggregation rapidly promotes the emergence of defective interfering particles. Therefore, virion aggregation provides immediate fitness benefits to the virus but incurs fitness costs after a few viral generations. This suggests that an optimal strategy for the virus is to undergo virion aggregation only episodically, for instance, during interhost transmission. IMPORTANCE Recent insights have revealed that viruses use a highly diverse set of strategies to release multiple viral genomes into the same target cells, allowing the emergence of beneficial, but also detrimental, interactions among viruses inside infected cells. This has prompted interest among microbial ecologists and evolutionary biologists in studying how collective dispersal impacts the outcome of viral infections. Here, we have used vesicular stomatitis virus as a model system to study the evolutionary implications of collective dissemination mediated by viral aggregates, since this virus can spontaneously aggregate in the presence of saliva. We find that saliva-driven aggregation has a dual effect on viral fitness; whereas aggregation tends to increase infectivity in the very short term, virion aggregates are highly susceptible to invasion by noncooperative defective variants after a few viral generations.

scholarly journals Incomplete influenza A virus genomes are abundant but readily complemented during spatially structured viral spread

2019 ◽  
Author(s):  
Nathan T. Jacobs ◽  
Nina O. Onuoha ◽  
Alice Antia ◽  
Rustom Antia ◽  
John Steel ◽  
...  
Keyword(s):  
Influenza A ◽  
Mutant Virus ◽  
Viral Fitness ◽  
H3n2 Virus ◽  
Multiple Infection ◽  
Mixed System ◽  
Viral Genomes ◽  
Viral Spread ◽  
A Cell

AbstractViral genomes comprising multiple distinct RNA segments can undergo genetic exchange through reassortment, a process that facilitates viral evolution and can have major epidemiological consequences. Segmentation also allows the replication of incomplete viral genomes (IVGs), however, and evidence suggests that IVGs occur frequently for influenza A viruses. Here we quantified the frequency of IVGs using a novel single cell assay and then examined their implications for viral fitness. We found that each segment of influenza A/Panama/2007/99 (H3N2) virus has only a 58% probability of being present in a cell infected with a single virion. These observed frequencies accurately account for the abundant reassortment seen in co-infection, and suggest that an average of 3.7 particles are required for replication of a full viral genome in a cell. This dependence on multiple infection is predicted to decrease infectivity and to slow viral propagation in a well-mixed system. Importantly, however, modeling of spatially structured viral growth predicted that the need for complementation is met more readily when secondary spread occurs locally. This expectation was supported by experimental infections in which the level spatial structure was manipulated. Furthermore, a virus engineered to be entirely dependent on co-infection to replicate in vivo was found to grow robustly in guinea pigs, suggesting that coinfection is sufficiently common in vivo to support propagation of IVGs. The infectivity of this mutant virus was, however, reduced 815-fold relative wild-type and the mutant virus did not transmit to contacts. Thus, while incomplete genomes augment reassortment and contribute to within-host spread, the existence of rare complete IAV genomes may be critical for transmission to new hosts.

scholarly journals TRIM22. A Multitasking Antiviral Factor

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1864
Author(s):  
Isabel Pagani ◽  
Guido Poli ◽  
Elisa Vicenzi
Keyword(s):  
Protein Interactions ◽  
Influenza A ◽  
Direct Interaction ◽  
Type I Interferons ◽  
Viral Gene ◽  
Target Cells ◽  
Type I ◽  
Protein Protein Interactions ◽  
Viral Genomes ◽  
Dna And Rna

Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.

scholarly journals Genomic epidemiology reveals multiple introductions of SARS-CoV-2 followed by community and nosocomial spread, Germany, February to May 2020

2021 ◽  
Vol 26 (43) ◽  
Author(s):  
Maximilian Muenchhoff ◽  
Alexander Graf ◽  
Stefan Krebs ◽  
Caroline Quartucci ◽  
Sandra Hasmann ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Sequence Data ◽  
Phylogenetic Analyses ◽  
Local Level ◽  
University Hospital ◽  
Metropolitan Region ◽  
Viral Genomes ◽  
Genomic Epidemiology ◽  
Viral Spread ◽  
Spatio Temporal

Background In the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data. Aim We applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata. Methods We investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission. Results We identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions. Conclusions Early spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.

scholarly journals A putative antiviral role of plant cytidine deaminases

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 622
Author(s):  
Susana Martín ◽  
José M. Cuevas ◽  
Ana Grande-Pérez ◽  
Santiago F. Elena
Keyword(s):  
Mammalian Cells ◽  
Mutagenic Activity ◽  
Population Diversity ◽  
Viral Fitness ◽  
Cauliflower Mosaic Virus ◽  
Cytidine Deaminases ◽  
Viral Genomes ◽  
Mutational Spectra ◽  
Antiviral Mechanism

Background: A mechanism of innate antiviral immunity operating against viruses infecting mammalian cells has been described during the last decade.  Host cytidine deaminases (e.g., APOBEC3 proteins) edit viral genomes, giving rise to hypermutated nonfunctional viruses; consequently, viral fitness is reduced through lethal mutagenesis.  By contrast, sub-lethal hypermutagenesis may contribute to virus evolvability by increasing population diversity.  To prevent genome editing, some viruses have evolved proteins that mediate APOBEC3 degradation.  The model plant Arabidopsis thaliana genome encodes nine cytidine deaminases (AtCDAs), raising the question of whether deamination is an antiviral mechanism in plants as well. Methods: Here we tested the effects of expression of AtCDAs on the pararetrovirus Cauliflower mosaic virus (CaMV). Two different experiments were carried out. First, we transiently overexpressed each one of the nine A. thaliana AtCDA genes in Nicotiana bigelovii plants infected with CaMV, and characterized the resulting mutational spectra, comparing them with those generated under normal conditions.  Secondly, we created A. thaliana transgenic plants expressing an artificial microRNA designed to knock-out the expression of up to six AtCDA genes.  This and control plants were then infected with CaMV.  Virus accumulation and mutational spectra where characterized in both types of plants. Results:  We have shown that the A. thaliana AtCDA1 gene product exerts a mutagenic activity, significantly increasing the number of G to A mutations in vivo, with a concomitant reduction in the amount of CaMV genomes accumulated.  Furthermore, the magnitude of this mutagenic effect on CaMV accumulation is positively correlated with the level of AtCDA1 mRNA expression in the plant. Conclusions: Our results suggest that deamination of viral genomes may also work as an antiviral mechanism in plants.

scholarly journals CD8+ T Lymphocytes Mediate Borna Disease Virus-Induced Immunopathology Independently of Perforin

2001 ◽  
Vol 75 (21) ◽  
pp. 10460-10466 ◽  
Author(s):  
Jürgen Hausmann ◽  
Karin Schamel ◽  
Peter Staeheli
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Disease Virus ◽  
Target Cells ◽  
Wild Type ◽  
Pathogenic Potential ◽  
Borna Disease Virus ◽  
Viral Spread ◽  
Deficient Mice ◽  
Borna Disease

ABSTRACT Perforin-mediated lysis of target cells is the major antiviral effector mechanism of CD8+ T lymphocytes. We have analyzed the role of perforin in a mouse model for CD8+T-cell-mediated central nervous system (CNS) immunopathology induced by Borna disease virus. When a defective perforin gene was introduced into the genetic background of the Borna disease-susceptible mouse strain MRL, the resulting perforin-deficient mice developed strong neurological disease in response to infection indistinguishable from that of their perforin-expressing littermates. The onset of disease was slightly delayed. Brains of diseased perforin-deficient mice showed similar amounts and a similar distribution of CD8+ T cells as wild-type animals. Perforin deficiency had no impact on the kinetics of viral spread through the CNS. Unlike brain lymphocytes from diseased wild-type mice, lymphocytes from perforin-deficient MRL mice showed no in vitro cytolytic activity towards target cells expressing the nucleoprotein of Borna disease virus. Taken together, these results demonstrate that CD8+ T cells mediate Borna disease independent of perforin. They further suggest that the pathogenic potential of CNS-infiltrating CD8+ T cells does not primarily reside in their lytic activity but rather in other functions.

Differential expression and activity of the porcine type I interferon family

2010 ◽  
Vol 42 (2) ◽  
pp. 248-258 ◽  
Author(s):  
Yongming Sang ◽  
Raymond R. R. Rowland ◽  
Richard A. Hesse ◽  
Frank Blecha
Keyword(s):  
Antiviral Activity ◽  
Expression Profiles ◽  
Type I Interferons ◽  
Respiratory Syndrome Virus ◽  
Target Cells ◽  
Type I ◽  
Antiviral Responses ◽  
Type I Ifns ◽  
Antiviral Activities ◽  
Vesicular Stomatitis

Type I interferons (IFNs) are central to innate and adaptive immunity, and many have unique developmental and physiological functions. However, in most species, only two subtypes, IFN-α and IFN-β, have been well studied. Because of the increasing importance of zoonotic viral diseases and the use of pigs to address human research questions, it is important to know the complete repertoire and activity of porcine type I IFNs. Here we show that porcine type I IFNs comprise at least 39 functional genes distributed along draft genomic sequences of chromosomes 1 and 10. These functional IFN genes are classified into 17 IFN-α subtypes, 11 IFN-δ subtypes, 7 IFN-ω subtypes, and single-subtype subclasses of IFN-αω, IFN-β, IFN-ε, and IFN-κ. We found that porcine type I IFNs have diverse expression profiles and antiviral activities against porcine reproductive and respiratory syndrome virus (PRRSV) and vesicular stomatitis virus (VSV), with activity ranging from 0 to >105 U·ng−1·ml−1. Whereas most IFN-α subtypes retained the greatest antiviral activity against both PRRSV and VSV in porcine and MARC-145 cells, some IFN-δ and IFN-ω subtypes, IFN-β, and IFN-αω differed in their antiviral activity based on target cells and viruses. Several IFNs, including IFN-α7/11, IFN-δ2/7, and IFN-ω4, exhibited minimal or no antiviral activity in the tested target cell-virus systems. Thus comparative studies showed that antiviral activity of porcine type I IFNs is virus- and cell-dependent, and IFN-αs are positively correlated with induction of MxA, an IFN-stimulated gene. Collectively, these data provide fundamental genomic information for porcine type I IFNs, information that is necessary for understanding porcine physiological and antiviral responses.

scholarly journals Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission

2013 ◽  
Vol 210 (13) ◽  
pp. 2813-2821 ◽  
Author(s):  
Marine Malbec ◽  
Françoise Porrot ◽  
Rejane Rua ◽  
Joshua Horwitz ◽  
Florian Klein ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Target Cells ◽  
Type I ◽  
Broadly Neutralizing Antibodies ◽  
Major Mechanism ◽  
Viral Spread ◽  
Cell Transmission ◽  
Cd4 Binding Site ◽  
Virological Synapses ◽  
Hiv 1

The neutralizing activity of anti–HIV-1 antibodies is typically measured in assays where cell-free virions enter reporter cell lines. However, HIV-1 cell to cell transmission is a major mechanism of viral spread, and the effect of the recently described broadly neutralizing antibodies (bNAbs) on this mode of transmission remains unknown. Here we identify a subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes. These antibodies target either the CD4-binding site (NIH45-46 and 3BNC60) or the glycan/V3 loop (10-1074 and PGT121) on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. These antibodies accumulate at virological synapses and impair the clustering and fusion of infected and target cells and the transfer of viral material to uninfected T cells. In addition, they block viral cell to cell transmission to plasmacytoid DCs and thereby interfere with type-I IFN production. Thus, only a subset of bNAbs can efficiently prevent HIV-1 cell to cell transmission, and this property should be considered an important characteristic defining antibody potency for therapeutic or prophylactic antiviral strategies.

scholarly journals TMPRSS2 and TMPRSS4 Facilitate Trypsin-Independent Spread of Influenza Virus in Caco-2 Cells

2010 ◽  
Vol 84 (19) ◽  
pp. 10016-10025 ◽  
Author(s):  
Stephanie Bertram ◽  
Ilona Glowacka ◽  
Paulina Blazejewska ◽  
Elizabeth Soilleux ◽  
Paul Allen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Serine Proteases ◽  
Alveolar Epithelium ◽  
Influenza Viruses ◽  
Target Cells ◽  
Human Respiratory Tract ◽  
Proteolytic Activation ◽  
Viral Spread ◽  
Endogenous Expression ◽  
Influenza Virus Hemagglutinin

ABSTRACT Proteolysis of influenza virus hemagglutinin by host cell proteases is essential for viral infectivity, but the proteases responsible are not well defined. Recently, we showed that engineered expression of the type II transmembrane serine proteases (TTSPs) TMPRSS2 and TMPRSS4 allows hemagglutinin (HA) cleavage. Here we analyzed whether TMPRSS2 and TMPRSS4 are expressed in influenza virus target cells and support viral spread in the absence of exogenously added protease (trypsin). We found that transient expression of TMPRSS2 and TMPRSS4 resulted in HA cleavage and trypsin-independent viral spread. Endogenous expression of TMPRSS2 and TMPRSS4 in cell lines correlated with the ability to support the spread of influenza virus in the absence of trypsin, indicating that these proteases might activate influenza virus in naturally permissive cells. Indeed, RNA interference (RNAi)-mediated knockdown of both TMPRSS2 and TMPRSS4 in Caco-2 cells, which released fully infectious virus without trypsin treatment, markedly reduced the spread of influenza virus, demonstrating that these proteases were responsible for efficient proteolytic activation of HA in this cell line. Finally, TMPRSS2 was found to be coexpressed with the major receptor determinant of human influenza viruses, 2,6-linked sialic acids, in human alveolar epithelium, indicating that viral target cells in the human respiratory tract express TMPRSS2. Collectively, our results point toward an important role for TMPRSS2 and possibly TMPRSS4 in influenza virus replication and highlight the former protease as a potential therapeutic target.

scholarly journals Recognition of viral glycoproteins by influenza A-specific cross-reactive cytolytic T lymphocytes.

1980 ◽  
Vol 151 (4) ◽  
pp. 945-958 ◽  
Author(s):  
U H Koszinowski ◽  
H Allen ◽  
M J Gething ◽  
M D Waterfield ◽  
H D Klenk
Keyword(s):  
T Lymphocytes ◽  
Influenza A ◽  
Type A ◽  
Lipid Vesicles ◽  
Influenza Viruses ◽  
M Protein ◽  
Antigenic Determinants ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Viral Glycoproteins

Two populations of cytolytic T lymphocytes (CTL) generated after influenza A virus infection can be distinguished into one with specificity for the sensitizing hemagglutinin type and a second with cross-reactivity for antigens induced by other type-A influenza viruses. The molecules carrying the antigenic determinants recognized by the cross-reactive CTL were studied. In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane. These target cells were lysed by cross-reactive CTL. The envelope proteins of type A/Victoria virus were separated from the other virion components and reconstituted into lipid vesicles that lacked M protein that subsequently were used to prepare artificial target cells. Target-cell formation with vesicles was achieved by addition of fusion-active Sendai virus. These artificial target cells were also susceptible to lysis by cross-reactive CTL. In contrast to previous observations that suggested that the M protein of influenza viruses is recognized by these effector cells, we present evidence that the antigencic determinants induced by the viral glycoproteins are recognized.

Sign in / Sign up

Export Citation Format

Share Document