scholarly journals The m6A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay

2021 ◽  
Author(s):  
Daniel Macveigh-Fierro ◽  
Angelina Cicerchia ◽  
Ashley Cadorette ◽  
Vasudha Sharma ◽  
Mandy Muller
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Kaposi Sarcoma ◽  
Lytic Infection ◽  
Mrna Abundance ◽  
Viral Mrna ◽  
Rna Modifications ◽  
Kshv Infection ◽  
Major Shift ◽  
Shed Light

The role m6A modifications have increasingly been associated with diverse set of roles in modulating viruses and influencing the outcomes of viral infection. Here we report that the landscape of m6A deposition is drastically shifted during KSHV (Kaposi Sarcoma Associated herpesvirus) lytic infection for both viral and host transcripts. In line with previous reports, we also saw an overall decrease in host methylation in favor of viral mRNA along with 5' hypomethylation and 3' hypermethylation. During KSHV lytic infection, a major shift in overall mRNA abundance is driven by the viral endoribonuclease SOX, which induces the decay of greater than 70% of transcripts. Here, we reveal that Interlukin-6 (IL-6) mRNA, a well-characterized SOX-resistant transcript, is m6A modified during lytic infection. Furthermore, we show that this modification falls within the IL-6 SOX Resistance Element (SRE), an RNA element in IL-6 3' UTR that was previously shown to be sufficient for protection from SOX cleavage. We show that the presence of this m6A modification is essential to confer SOX resistance to the IL-6 mRNA. We next show that this modification recruits the m6A reader YTHDC2 and found that YTHDC2 is necessary for the escape of the IL-6 transcript. These results shed light on how the host cell has evolved to use RNA modifications to circumvent viral manipulation of RNA fate during KSHV infection.

scholarly journals Modelling Degradation and Replication Kinetics of the Zika Virus In Vitro Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 547
Author(s):  
Veronika Bernhauerová ◽  
Veronica V. Rezelj ◽  
Marco Vignuzzi
Keyword(s):  
Mathematical Model ◽  
Viral Infection ◽  
Host Cell ◽  
Decay Time ◽  
Zika Virus ◽  
Infectious Virus ◽  
Numerical Characterization ◽  
The Mathematical Model

Mathematical models of in vitro viral kinetics help us understand and quantify the main determinants underlying the virus–host cell interactions. We aimed to provide a numerical characterization of the Zika virus (ZIKV) in vitro infection kinetics, an arthropod-borne emerging virus that has gained public recognition due to its association with microcephaly in newborns. The mathematical model of in vitro viral infection typically assumes that degradation of extracellular infectious virus proceeds in an exponential manner, that is, each viral particle has the same probability of losing infectivity at any given time. We incubated ZIKV stock in the cell culture media and sampled with high frequency for quantification over the course of 96 h. The data showed a delay in the virus degradation in the first 24 h followed by a decline, which could not be captured by the model with exponentially distributed decay time of infectious virus. Thus, we proposed a model, in which inactivation of infectious ZIKV is gamma distributed and fit the model to the temporal measurements of infectious virus remaining in the media. The model was able to reproduce the data well and yielded the decay time of infectious ZIKV to be 40 h. We studied the in vitro ZIKV infection kinetics by conducting cell infection at two distinct multiplicity of infection and measuring viral loads over time. We fit the mathematical model of in vitro viral infection with gamma distributed degradation time of infectious virus to the viral growth data and identified the timespans and rates involved within the ZIKV-host cell interplay. Our mathematical analysis combined with the data provides a well-described example of non-exponential viral decay dynamics and presents numerical characterization of in vitro infection with ZIKV.

scholarly journals Latent KSHV infection increases the vascular permeability of human endothelial cells

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5344-5354 ◽  
Author(s):  
Christophe Guilluy ◽  
Zhigang Zhang ◽  
Prasanna M. Bhende ◽  
Lisa Sharek ◽  
Ling Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Latent Infection ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Cell Junctions ◽  
Paracrine Factors ◽  
Kshv Infection ◽  
Multicentric Castleman Disease

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is associated with 3 different human malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Endothelial cells with latent KSHV infection display increased Rac1 activation and activation of its downstream modulator, p21-activated kinase 1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine phosphorylation of vascular endothelial (VE)–cadherin and β-catenin, whereas total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that KSHV-infected endothelial cells displayed increased permeability compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of reactive oxygen species (ROS) resulted in decreased permeability in the KSHV-infected endothelial cells. We further demonstrate that the KSHV K1 protein can activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1 activity in endothelial cells, resulting in the phosphorylation of VE-cadherin and β-catenin and leading to the disassembly of cell junctions and to increased vascular permeability of the infected endothelial cells.

scholarly journals Efficacy of Garlic and Onion against virus

2019 ◽  
Vol 10 (4) ◽  
pp. 3578-3586 ◽  
Author(s):  
Neha Sharma
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Antiviral Effect ◽  
Viral Assembly ◽  
Organosulfur Compounds ◽  
Phospholipid Membrane ◽  
Safe Alternative ◽  
Virus Attachment ◽  
Current Scenario ◽  
Pass Through

In the current scenario, pharmaceutical industry is dependent on chemical based drugs to treat viral infection. However, these drugs are known to induce many side effects in human body. There is pressing need to promote safe alternative to chemical based antiviral drugs. Onion and garlic are natural sources which are known to possess antiviral properties. It is well known that onion and garlic are rich source of organosulfur compounds. Organosulfur compounds like quercetin and allicin are associated with inhibition of viral infection. These chemicals can hinder virus attachment to host cell, alter transcription and translation of viral genome in host cell and also affect viral assembly. Quercetin can affect entry and attachment of Enterovirus and Influenza virus on host cell. This compound also has ability to inhibit RNA polymerase which is necessary for viral replication. Quercetin also inhibit process by which virus alter signalling pathway in host cell. Organosulfur compounds like allicin, diallyl trisulfide and ajoene are main chemicals which impart antiviral property to garlic. It is known that allicin can pass through phospholipid membrane of cell and can further contribute in inhibiting viral multiplication. Considering numerous studies which corroborate antiviral effect of onion and garlic, this paper recommends consumption of these plants as a safe alternative to prevent virus infection.

scholarly journals Global Transcriptional Responses of Pseudomonas aeruginosa to Phage PRR1 Infection

2007 ◽  
Vol 82 (5) ◽  
pp. 2324-2329 ◽  
Author(s):  
Janne J. Ravantti ◽  
Tanja M. Ruokoranta ◽  
A. Marika Alapuranen ◽  
Dennis H. Bamford
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Viral Infection ◽  
Host Cell ◽  
Cell Function ◽  
Growth Conditions ◽  
Growth Cycle ◽  
Global Changes ◽  
Mrna Levels ◽  
Transcriptional Responses ◽  
Number Of Genes

ABSTRACT The infectious cycles of viruses are known to cause dramatic changes to host cell function. The development of microarray technology has provided means to monitor host cell responses to viral infection at the level of global changes in mRNA levels. We have applied this methodology to investigate gene expression changes caused by a small, icosahedral, single-stranded-RNA phage, PRR1 (a member of the Leviviridae family), on its host, Pseudomonas aeruginosa, at different times during its growth cycle. Viral infection in this system resulted in changes in expression levels of <4% of P. aeruginosa genes. Interestingly, the number of genes affected by viral infection was significantly lower than the number of genes affected by changes in growth conditions during the experiment. Compared with a similar study that focused on the complex, double-stranded-DNA bacterial virus PRD1, it was evident that there were no universal responses to viral infection. However, in both cases, translation was affected in infected cells.

scholarly journals Zika in the Brain: New Models Shed Light on Viral Infection

2016 ◽  
Vol 22 (8) ◽  
pp. 639-641 ◽  
Author(s):  
Heather D. Hickman ◽  
Theodore C. Pierson
Keyword(s):  
Viral Infection ◽  
New Models ◽  
The Brain ◽  
Shed Light

Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination

1983 ◽  
Vol 3 (7) ◽  
pp. 1212-1221 ◽  
Author(s):  
A Babich ◽  
L T Feldman ◽  
J R Nevins ◽  
J E Darnell ◽  
C Weinberger
Keyword(s):  
Protein Synthesis ◽  
Host Cell ◽  
Cellular Protein ◽  
Host Protein ◽  
Cell Protein ◽  
Viral Mrna ◽  
Initiation Of Translation ◽  
Viral Mutant ◽  
Cellular Mrnas ◽  
Cellular Protein Synthesis

We have studied the adenovirus-induced inhibition of host cell protein synthesis and the effect of infection on the overall metabolism of host cell mRNA during the late phase of adenovirus infection by following the fate of a number of cellular mRNAs complementary to specific cloned DNA segments. At a time in infection when the rate of total cellular protein synthesis is drastically (greater than 90%) reduced, transcription of specific cellular genes is undiminished. However, the transport of newly synthesized cellular mRNA to the cytoplasm is greatly decreased. This decreased appearance of new mRNA in the cytoplasm cannot account for the observed cessation of cell specific protein synthesis, however, since the concentration of several preexisting cellular mRNAs, including the mRNA for actin, remains unchanged throughout the course of infection. The preexisting mRNA is intact, capped, and functional as judged by its ability to direct protein synthesis in vitro in a cap-dependent fashion. The interruption in host translation appears to operate at the level of initiation directly, since we find that fewer ribosomes are associated with a given cellular mRNA after infection than before infection. Furthermore, the in vivo inhibition of cellular protein synthesis does not appear to be the result of competition with viral mRNA, since conditions which prevent the efficient initiation of translation of viral mRNA (infection with a viral mutant) do not result in the recovery of cell translation. Thus, it appears that a late adenovirus gene product directly mediates a shutoff of host protein synthesis.

Ayurvedic system a new possible safe and effective way to get rid of this critical nCOVID-19 pandemic situation- A review

2021 ◽  
Vol 07 ◽  
Author(s):  
Sumel Ashique ◽  
Navjot K Sandhu
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Viral Infection ◽  
Traditional Medicine ◽  
Host Cell ◽  
Western Medicine ◽  
Treatment Strategies ◽  
Unani Medicine ◽  
System A ◽  
The World

: The nCOVID-19 virus has become the most threatening infections disease all over the world. From the beginning till today a large number of researches is going on to develop appropriate therapeutics that can prevent and cure this viral infection successfully. But unfortunately, modern western medicine could not find any effective drug having no toxic effects on host cell. TCM (traditional Chinese Medicine) has shown promising effect against nCOVID-19. This TCM contains natural occurring herbal decoctions which showed promising blocking of viral progression in host cell. These ayurvedic formulations containing homeopathic medicine, unani medicine and yoga to challenge the virus. The traditional medicine system is unable to cure properly but it can be a possible preventing strategy to stop this virus pandemicity. This review focuses how the ayurvedic medicines, homeopathic treatment strategies and yoga can impact to prevent the viral infection.

scholarly journals Hijacking of Lipid Droplets by Hepatitis C, Dengue and Zika Viruses—From Viral Protein Moonlighting to Extracellular Release

2020 ◽  
Vol 21 (21) ◽  
pp. 7901 ◽  
Author(s):  
Alexandra P.M. Cloherty ◽  
Andrea D. Olmstead ◽  
Carla M.S. Ribeiro ◽  
François Jean
Keyword(s):  
Hepatitis C ◽  
Viral Infection ◽  
Host Cell ◽  
Lipid Droplets ◽  
Viral Proteins ◽  
Biological Properties ◽  
Protein Functions ◽  
Associated Proteins ◽  
Viral Lifecycle ◽  
Moonlighting Functions

Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. Flaviviridae members, including hepatitis C, dengue and Zika viruses, extensively manipulate host lipid metabolism, underlining the importance of lipid droplets (LDs) in viral infection. LDs are dynamic cytoplasmic organelles that can act as sequestration platforms for a unique subset of host and viral proteins. Transient recruitment and mobilization of proteins to LDs during viral infection impacts host-cell biological properties, LD functionality and canonical protein functions. Notably, recent studies identified LDs in the nucleus and also identified that LDs are transported extracellularly via an autophagy-mediated mechanism, indicating a novel role for autophagy in Flaviviridae infections. These developments underline an unsuspected diversity and localization of LDs and potential moonlighting functions of LD-associated proteins during infection. This review summarizes recent breakthroughs concerning the LD hijacking activities of hepatitis C, dengue and Zika viruses and potential roles of cytoplasmic, nuclear and extracellular LD-associated viral proteins during infection.

scholarly journals African Swine Fever Virus Blocks the Host Cell Antiviral Inflammatory Response through a Direct Inhibition of PKC-θ-Mediated p300 Transactivation

2008 ◽  
Vol 83 (2) ◽  
pp. 969-980 ◽  
Author(s):  
Aitor G. Granja ◽  
Elena G. Sánchez ◽  
Prado Sabina ◽  
Manuel Fresno ◽  
Yolanda Revilla
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Viral Infection ◽  
Host Cell ◽  
Expression Pattern ◽  
African Swine Fever Virus ◽  
Gene Expression Pattern ◽  
African Swine Fever ◽  
Fever Virus ◽  
Amino Terminal

ABSTRACT During a viral infection, reprogramming of the host cell gene expression pattern is required to establish an adequate antiviral response. The transcriptional coactivators p300 and CREB binding protein (CBP) play a central role in this regulation by promoting the assembly of transcription enhancer complexes to specific promoters of immune and proinflammatory genes. Here we show that the protein A238L encoded by African swine fever virus counteracts the host cell inflammatory response through the control of p300 transactivation during the viral infection. We demonstrate that A238L inhibits the expression of the inflammatory regulators cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-α) by preventing the recruitment of p300 to the enhanceosomes formed on their promoters. Furthermore, we report that A238L inhibits p300 activity during the viral infection and that its amino-terminal transactivation domain is essential in the A238L-mediated inhibition of the inflammatory response. Importantly, we found that the residue serine 384 of p300 is required for the viral protein to accomplish its inhibitory function and that ectopically expressed PKC-θ completely reverts this inhibition, thus indicating that this signaling pathway is disrupted by A238L during the viral infection. Furthermore, we show here that A238L does not affect PKC-θ enzymatic activity, but the molecular mechanism of this viral inhibition relies on the lack of interaction between PKC-θ and p300. These findings shed new light on how viruses alter the host cell antiviral gene expression pattern through the blockade of the p300 activity, which represents a new and sophisticated viral mechanism to evade the inflammatory and immune defense responses.

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