Repulsion effect on superinfecting virions by infected cells for virus infection dynamic model with absorption effect and chemotaxis

In mammals the interferon (IFN) system is a central innate antiviral defence mechanism, while the involvement of RNA interference (RNAi) in antiviral response against RNA viruses is uncertain. Here, we tested whether RNAi is involved in the antiviral response in mammalian cells. To investigate the role of RNAi in influenza A virus-infected cells in the absence of IFN, we used Vero cells that lack IFN-α and IFN-β genes. Our results demonstrate that knockdown of a key RNAi component, Dicer, led to a modest increase of virus production and accelerated apoptosis of influenza A virus-infected cells. These effects were much weaker in the presence of IFN. The results also show that in both Vero cells and the IFN-producing alveolar epithelial A549 cell line influenza A virus targets Dicer at mRNA and protein levels. Thus, RNAi is involved in antiviral response, and Dicer is important for protection against influenza A virus infection.

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Human IFITM3 restricts Chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction

10.1101/2020.09.11.292946 ◽

2020 ◽

Author(s):

Sergej Franz ◽

Thomas Zillinger ◽

Fabian Pott ◽

Christiane Schüler ◽

Sandra Dapa ◽

...

Keyword(s):

Virus Infection ◽

Influenza A ◽

Chikungunya Virus ◽

Protein S ◽

Human Cells ◽

Structural Protein ◽

Infected Cells ◽

Mayaro Virus ◽

The Impact

AbstractInterferon-induced transmembrane (IFITM) proteins restrict infection by enveloped viruses through interfering with membrane fusion and virion internalisation. The role of IFITM proteins during alphaviral infection of human cells and viral counteraction strategies remain largely unexplored. Here, we characterized the impact of IFITM proteins and variants on entry and spread of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in human cells, and provide first evidence for a CHIKV-mediated antagonism of IFITM proteins. IFITM1, 2 and 3 restricted infection at the level of alphavirus glycoprotein-mediated entry, both in the context of direct infection and during cell-to-cell transmission. Relocalization of normally endosomal IFITM3 to the plasma membrane resulted in the loss of its antiviral activity. rs12252-C, a naturally occurring variant of IFITM3 that has been proposed to associate with severe influenza in humans, restricted CHIKV, MAYV and influenza A virus infection as efficiently as wild-type IFITM3. Finally, all antivirally active IFITM variants displayed reduced cell surface levels in CHIKV-infected cells involving a posttranscriptional process mediated by one or several non-structural protein(s) of CHIKV.

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Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein

Journal of Virology ◽

10.1128/jvi.01779-16 ◽

2016 ◽

Vol 91 (5) ◽

Cited By ~ 12

Author(s):

Anthony Khong ◽

Craig H. Kerr ◽

Clarence H. L. Yeung ◽

Kathleen Keatings ◽

Arabinda Nayak ◽

...

Keyword(s):

Virus Infection ◽

Stress Granule ◽

Granule Formation ◽

Viral Translation ◽

Content Type ◽

Cellular Processes ◽

Cellular Environment ◽

Viral Yield ◽

Infected Cells ◽

Paralysis Virus

ABSTRACT Stress granules (SGs) are cytosolic ribonucleoprotein aggregates that are induced during cellular stress. Several viruses modulate SG formation, suggesting that SGs have an impact on virus infection. However, the mechanisms and impact of modulating SG assembly in infected cells are not completely understood. In this study, we identify the dicistrovirus cricket paralysis virus 1A (CrPV-1A) protein that functions to inhibit SG assembly during infection. Moreover, besides inhibiting RNA interference, CrPV-1A also inhibits host transcription, which indirectly modulates SG assembly. Thus, CrPV-1A is a multifunctional protein. We identify a key R146A residue that is responsible for these effects, and mutant CrPV(R146A) virus infection is attenuated in Drosophila melanogaster S2 cells and adult fruit flies and results in increased SG formation. Treatment of CrPV(R146A)-infected cells with actinomycin D, which represses transcription, restores SG assembly suppression and viral yield. In summary, CrPV-1A modulates several cellular processes to generate a cellular environment that promotes viral translation and replication. IMPORTANCE RNA viruses encode a limited set of viral proteins to modulate an array of cellular processes in order to facilitate viral replication and inhibit antiviral defenses. In this study, we identified a viral protein, called CrPV-1A, within the dicistrovirus cricket paralysis virus that can inhibit host transcription, modulate viral translation, and block a cellular process called stress granule assembly. We also identified a specific amino acid within CrPV-1A that is important for these cellular processes and that mutant viruses containing mutations of CrPV-1A attenuate virus infection. We also demonstrate that the CrPV-1A protein can also modulate cellular processes in human cells, suggesting that the mode of action of CrPV-1A is conserved. We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellular environment in virus-infected cells that permits productive virus infection.

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ANTIBODY-INDUCED MODULATION OF VIRAL ANTIGENS FROM INFECTED CELLS: BIOLOGICAL AND MOLECULAR STUDIES OF MEASLES VIRUS INFECTION AND IMPLICATIONS FOR UNDERSTANDING VIRUS PERSISTENCE AND RECEPTOR DISEASES

Animal Virus Genetics ◽

10.1016/b978-0-12-255850-4.50070-6 ◽

1980 ◽

pp. 769-790

Author(s):

Robert S. Fujinami ◽

Michael B.A. Oldstone

Keyword(s):

Virus Infection ◽

Measles Virus ◽

Virus Persistence ◽

Viral Antigens ◽

Molecular Studies ◽

Infected Cells

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Coexistence and Noncoexistence of Markovian Viruses and their Hosts

Journal of Applied Probability ◽

10.1239/jap/1395771423 ◽

2014 ◽

Vol 51 (1) ◽

pp. 191-208 ◽

Cited By ~ 2

Author(s):

Jakob E. Björnberg ◽

Erik I. Broman

Keyword(s):

Virus Infection ◽

Predator Prey ◽

Classic Problem ◽

Infected Cells ◽

Predator Prey Models ◽

Two Populations ◽

Competing Populations

Examining possibilities for the coexistence of two competing populations is a classic problem which dates back to the earliest ‘predator-prey’ models. In this paper we study this problem in the context of a model introduced in Björnberg et al. (2012) for the spread of a virus infection in a population of healthy cells. The infected cells may be seen as a population of ‘predators’ and the healthy cells as a population of ‘prey’. We show that, depending on the parameters defining the model, there may or may not be coexistence of the two populations, and we give precise criteria for this.

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Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update

Metabolites ◽

10.3390/metabo10090356 ◽

2020 ◽

Vol 10 (9) ◽

pp. 356 ◽

Cited By ~ 1

Author(s):

David Balgoma ◽

Luis Gil-de-Gómez ◽

Olimpio Montero

Keyword(s):

Lipid Metabolism ◽

Virus Infection ◽

Host Cell ◽

Viral Infections ◽

Virus Entry ◽

Pathogenic Mechanisms ◽

Cell Lipid ◽

Ssrna Virus ◽

Infected Cells

The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection.

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Mitochondrial Import of Dengue Virus NS3 Protease and Cleavage of GrpEL1, a Cochaperone of Mitochondrial Hsp70

Journal of Virology ◽

10.1128/jvi.01178-20 ◽

2020 ◽

Vol 94 (17) ◽

Author(s):

Chaitanya Gandikota ◽

Fareed Mohammed ◽

Lekha Gandhi ◽

Deepti Maisnam ◽

Ushodaya Mattam ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Severe Dengue ◽

Clinical Samples ◽

Mitochondrial Matrix ◽

Virus Infections ◽

Mitochondrial Import ◽

Mitochondrial Transport ◽

Infected Cells ◽

Mitochondrial Hsp70

ABSTRACT Dengue virus infections, which have been reported in nearly 140 countries, pose a significant threat to human health. The genome of dengue virus encodes three structural and seven nonstructural (NS) proteins along with two untranslated regions, one each on both ends. Among them, dengue protease (NS3) plays a pivotal role in polyprotein processing and virus multiplication. NS3 is also known to regulate several host proteins to induce and maintain pathogenesis. Certain viral proteins are known to interact with mitochondrial membrane proteins and interfere with their functions, but the association of a virus-coded protein with the mitochondrial matrix is not known. In this report, by using in silico analysis, we show that NS3pro alone is capable of mitochondrial import; however, this is dependent on its innate mitochondrial transport signal (MTS). Transient-transfection and protein import studies confirm the import of NS3pro to the mitochondrial matrix. Similarly, NS3pro-helicase (amino acids 1 to 464 of NS3) also targets the mitochondria. Intriguingly, reduced levels of matrix-localized GrpE protein homolog 1 (GrpEL1), a cochaperone of mitochondrial Hsp70 (mtHsp70), were noticed in NS3pro-expressing, NS3pro-helicase-expressing, and virus-infected cells. Upon the use of purified components, GrpEL1 undergoes cleavage, and the cleavage sites have been mapped to KR81A and QR92S. Importantly, GrpEL1 levels are seriously compromised in severe dengue virus-infected clinical samples. Our studies provide novel insights into the import of NS3 into host mitochondria and identify a hitherto unknown factor, GrpEL1, as a cleavage target, thereby providing new avenues for dengue virus research and the design of potential therapeutics. IMPORTANCE Approximately 40% of the world’s population is at risk of dengue virus infection. There is currently no specific drug or potential vaccine for these infections. Lack of complete understanding of the pathogenesis of the virus is one of the hurdles that must be overcome in developing antivirals for this virus infection. In the present study, we observed that the dengue virus-coded protease imports to the mitochondrial matrix, and our report is the first ever of a virus-coded protein, either animal or human, importing to the mitochondrial matrix. Our analysis indicates that the observed mitochondrial import is due to an inherited mitochondrial transport signal. We also show that matrix-localized GrpE protein homolog 1 (GrpEL1), a cochaperone of mitochondrial Hsp70 (mtHsp70), is also the substrate of dengue virus protease, as observed in vitro and ex vivo in virus-infected cells and dengue virus-infected clinical samples. Hence, our studies reveal an essential aspect of the pathogenesis of dengue virus infections, which may aid in developing antidengue therapeutics.

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Vaccinia Virus Infection Disarms the Mitochondrion-Mediated Pathway of the Apoptotic Cascade by Modulating the Permeability Transition Pore

Journal of Virology ◽

10.1128/jvi.75.23.11437-11448.2001 ◽

2001 ◽

Vol 75 (23) ◽

pp. 11437-11448 ◽

Cited By ~ 44

Author(s):

Shawn T. Wasilenko ◽

Adrienne F. A. Meyers ◽

Kathleen Vander Helm ◽

Michele Barry

Keyword(s):

Virus Infection ◽

Vaccinia Virus ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Jurkat Cells ◽

Caspase 8 ◽

Apoptotic Pathway ◽

Vaccinia Virus Infection ◽

Infected Cells ◽

Apoptotic Cascade

ABSTRACT Many viruses have evolved strategies that target crucial components within the apoptotic cascade. One of the best studied is the caspase 8 inhibitor, crmA/Spi-2, encoded by members of the poxvirus family. Since many proapoptotic stimuli induce apoptosis through a mitochondrion-dependent, caspase 8-independent pathway, we hypothesized that vaccinia virus would encode a mechanism to directly modulate the mitochondrial apoptotic pathway. In support of this, we observed that Jurkat cells, which undergo Fas-mediated apoptosis exclusively through the mitochondrial route, were resistant to Fas-induced death following infection with a crmA/Spi-2-deficient strain of vaccinia virus. In addition, vaccinia virus-infected cells subjected to the proapoptotic stimulus staurosporine exhibited decreased levels of both cytochromec released from the mitochondria and caspase 3 activation. In all cases we found that the loss of the mitochondrial membrane potential, which occurs as a result of opening the multimeric permeability transition pore complex, was prevented in vaccinia virus-infected cells. Moreover, vaccinia virus infection specifically inhibited opening of the permeability transition pore following treatment with the permeability transition pore ligand atractyloside and t-butylhydroperoxide. These studies indicate that vaccinia virus infection directly impacts the mitochondrial apoptotic cascade by influencing the permeability transition pore.

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Coexistence and Noncoexistence of Markovian Viruses and their Hosts

Journal of Applied Probability ◽

10.1017/s0021900200010172 ◽

2014 ◽

Vol 51 (01) ◽

pp. 191-208 ◽

Cited By ~ 1

Author(s):

Jakob E. Björnberg ◽

Erik I. Broman

Keyword(s):

Virus Infection ◽

Predator Prey ◽

Classic Problem ◽

Infected Cells ◽

Predator Prey Models ◽

Two Populations ◽

Competing Populations

Examining possibilities for the coexistence of two competing populations is a classic problem which dates back to the earliest ‘predator-prey’ models. In this paper we study this problem in the context of a model introduced in Björnberg et al. (2012) for the spread of a virus infection in a population of healthy cells. The infected cells may be seen as a population of ‘predators’ and the healthy cells as a population of ‘prey’. We show that, depending on the parameters defining the model, there may or may not be coexistence of the two populations, and we give precise criteria for this.

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