scholarly journals Antiviral RNAi response against the insect-specific Agua Salud alphavirus

2021 ◽  
Author(s):  
Mine Altinli ◽  
Mayke Leggewie ◽  
Marlis Badusche ◽  
Rashwita Gyanwali ◽  
Christina Scherer ◽  
...  
Keyword(s):  
Rnai Pathway ◽  
Nucleotide Bias ◽  
Knock Out ◽  
Antiviral Responses ◽  
Ping Pong ◽  
Infected Cells ◽  
Sirna Pathway ◽  
Antiviral Role ◽  
Rnai Response

Arboviruses transmitted by mosquitoes are responsible for the death of millions of people each year. In addition to arboviruses, many insect-specific viruses (ISVs) have been discovered in mosquitoes in the last decade. ISVs, in contrast to arboviruses transmitted by mosquitoes to vertebrates, cannot replicate in vertebrate cells even when they are evolutionarily closely related to arboviruses. The alphavirus genus includes many arboviruses, although only a few ISVs have been discovered from this genus so far. Here, we investigate the interactions of a recently isolated insect-specific alphavirus, Agua-Salud alphavirus (ASALV), with its mosquito host. RNAi is one of the essential antiviral responses against arboviruses, although there is little knowledge on the interactions of RNAi with ISVs. Through knock-down of transcripts of the different key RNAi pathway (siRNA, miRNA and piRNA) proteins, we show the antiviral role of Ago2 (siRNA), Ago1 (miRNA), and Piwi4 proteins against ASALV in Aedes aegypti derived cells. ASALV replication increased in Dicer2 and Ago2 knock-out cells, confirming the antiviral role of the siRNA pathway. In infected cells, mainly ASALV-specific siRNAs are produced while piRNAs, with the characteristic nucleotide bias resulting from ping-pong amplification, are only produced in Dicer2 knock-out cells. Taken together, ASALV interactions with the mosquito RNAi response differs from arthropod-borne alphaviruses in some aspects, although they also share some commonalities. Further research is needed to understand whether the identified differences can be generalised to other insect-specific alphaviruses.

scholarly journals Knockdown of piRNA pathway proteins results in enhanced Semliki Forest virus production in mosquito cells

2013 ◽  
Vol 94 (7) ◽  
pp. 1680-1689 ◽  
Author(s):  
Esther Schnettler ◽  
Claire L. Donald ◽  
Stacey Human ◽  
Mick Watson ◽  
Ricky W. C. Siu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Semliki Forest Virus ◽  
Virus Production ◽  
Antiviral Responses ◽  
Mosquito Cells ◽  
Mosquito Cell Lines ◽  
Arbovirus Infection ◽  
Pirna Pathway ◽  
Sirna Pathway

The exogenous siRNA pathway is important in restricting arbovirus infection in mosquitoes. Less is known about the role of the PIWI-interacting RNA pathway, or piRNA pathway, in antiviral responses. Viral piRNA-like molecules have recently been described following infection of mosquitoes and derived cell lines with several arboviruses. The piRNA pathway has thus been suggested to function as an additional small RNA-mediated antiviral response to the known infection-induced siRNA response. Here we show that piRNA-like molecules are produced following infection with the naturally mosquito-borne Semliki Forest virus in mosquito cell lines. We show that knockdown of piRNA pathway proteins enhances the replication of this arbovirus and defines the contribution of piRNA pathway effectors, thus characterizing the antiviral properties of the piRNA pathway. In conclusion, arbovirus infection can trigger the piRNA pathway in mosquito cells, and knockdown of piRNA proteins enhances virus production.

scholarly journals Transcriptomic signature and metabolic programming of bovine classical and nonclassical monocytes indicate distinct functional specializations

2020 ◽  
Author(s):  
Stephanie C. Talker ◽  
G. Tuba Barut ◽  
Reto Rufener ◽  
Lilly von Münchow ◽  
Artur Summerfield
Keyword(s):  
Tissue Repair ◽  
Aerobic Glycolysis ◽  
Human Monocytes ◽  
Monocyte Subsets ◽  
Antiviral Responses ◽  
Functional Differences ◽  
Depth Analysis ◽  
Transcriptomic Signature ◽  
Antiviral Role

AbstractSimilar to human monocytes, bovine monocytes can be split into CD14+CD16− classical and CD14−CD16+ nonclassical monocytes (cM and ncM, respectively). Here, we present an in-depth analysis of their steady-state transcriptomes, highlighting pronounced functional specializations. Gene transcription indicates that pro-inflammatory and antibacterial processes are associated with cM, while ncM appear to be specialized in regulatory/anti-inflammatory functions and tissue repair, as well as antiviral responses and T-cell immunomodulation. In support of these functional differences, we found that oxidative phosphorylation prevails in ncM, whereas cM are clearly biased towards aerobic glycolysis. Furthermore, bovine monocyte subsets differed in their responsiveness to TLR ligands, supporting an antiviral role of ncM. Taken together, these data clearly indicate a variety of subset-specific functions in cM and ncM that are likely to be transferable to monocyte subsets of other species, including humans.

scholarly journals Human Cytomegalovirus miR-UL70-3p Downregulates the H2O2-Induced Apoptosis by Targeting the Modulator of Apoptosis-1 (MOAP1)

2021 ◽  
Vol 23 (1) ◽  
pp. 18
Author(s):  
Abhishek Pandeya ◽  
Raj Kumar Khalko ◽  
Anup Mishra ◽  
Nishant Singh ◽  
Sukhveer Singh ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Antiviral Responses ◽  
Persistent Infections ◽  
Innate Immune Mechanism ◽  
Infected Cells ◽  
Hcmv Replication ◽  
Induced Apoptosis

Human Cytomegalovirus (HCMV) is a prototypic beta herpesvirus, causing persistent infections in humans. There are medications that are used to treat the symptoms; however, there is no cure yet. Thus, understanding the molecular mechanisms of HCMV replication and its persistence may reveal new prevention strategies. HCMV evasive strategies on the antiviral responses of the human host largely rely on its significant portion of genome. Numerous studies have highlighted the importance of miRNA-mediated regulation of apoptosis, which is an innate immune mechanism that eradicates virus-infected cells. In this study, we explore the antiapoptotic role of hcmv-miR-UL70-3p in HEK293T cells. We establish that hcmv-miR-UL70-3p targets the proapoptotic gene Modulator of Apoptosis-1 (MOAP1) through interaction with its 3’UTR region of mRNA. The ectopic expression of hcmv-miR-UL70-3p mimic significantly downregulates the H2O2-induced apoptosis through the translational repression of MOAP1. Silencing of MOAP1 through siRNA also inhibits the H2O2-induced apoptosis, which further supports the hcmv-miR-UL70-3p mediated antiapoptotic effect by regulating MOAP1 expression. These results uncover a role for hcmv-miR-UL70-3p and its target MOAP1 in regulating apoptosis.

scholarly journals Antiviral Role of IFITM Proteins in Classical Swine Fever Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 126 ◽  
Author(s):  
Cheng Li ◽  
Hongqing Zheng ◽  
Yifan Wang ◽  
Wang Dong ◽  
Yaru Liu ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Mammalian Cells ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Infected Cells ◽  
The Relationship ◽  
Antiviral Role

The proteins IFITM1, IFITM2, and IFITM3 are host effectors against a broad range of RNA viruses whose roles in classical swine fever virus (CSFV) infection had not yet been reported. We investigated the effect of these proteins on CSFV replication in mammalian cells. The proteins were overexpressed and silenced using lentiviruses. Confocal microscopy was used to determine the distribution of these proteins in the cells, and immunofluorescence colocalization analysis was used to evaluate the relationship between IFITMs and the CSFV endosomal pathway, including early endosomes, late endosomes, and lysosomes. IFITM1, IFITM2, or IFITM3 overexpression significantly inhibited CSFV replication, whereas protein knockdown enhanced CSFV replication. In porcine alveolar macrophages (PAMs), IFITM1 was mainly located at the cell surface, whereas IFITM2 and IFITM3 were mainly located in the cytoplasm. Following CSFV infection, the distribution of IFITM1 changed. IFITM1, IFITM2, and IFITM3 colocalization with Lamp1, IFITM2 with Rab5 and Rab7, and IFITM3 with Rab7 were observed in CSFV-infected cells. Collectively, these results provide insights into the possible mechanisms associated with the anti-CSFV action of the IFITM family.

scholarly journals Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Brian Webster ◽  
Scott W Werneke ◽  
Biljana Zafirova ◽  
Sébastien This ◽  
Séverin Coléon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cell ◽  
Rna Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Virus Infections ◽  
Antiviral Responses ◽  
Infected Cells ◽  
Interferon Responses

Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections.

scholarly journals Density dependent enhancement effect ofWolbachiaand the host RNAi response to a densovirus inAedescells

2018 ◽  
Author(s):  
Rhys Parry ◽  
Cameron Bishop ◽  
Lachlan de Hayr ◽  
Sassan Asgari
Keyword(s):  
Enhancement Effect ◽  
Dependent Manner ◽  
Dna Virus ◽  
Dna Viruses ◽  
Density Dependent ◽  
Host Interaction ◽  
Ping Pong ◽  
Infected Cells ◽  
First Time ◽  
Rnai Response

AbstractThe endosymbiotic bacteriumWolbachia pipientishas been shown to restrict a range of RNA viruses inDrosophila melanogasterand transinfected dengue mosquito,Aedes aegypti. Here, we show thatWolbachiainfection enhances replication of Aedes albopictus densovirus (AalDNV-1), a single stranded DNA virus, inAedescell lines in a density-dependent manner. Analysis of previously produced small RNAs of Aag2 cells showed thatWolbachia-infected cells produced greater proportions of viral derived short interfering RNAs as compared to uninfected cells. Additionally, we found production of viral derived PIWI-like RNAs (vpiRNA) produced in response to AalDNV-1 infection. Nuclear fractions of Aag2 cells produced a primary vpiRNA signature U1bias whereas the typical “ping-pong” signature (U1- A10) was evident in the cytoplasmic fraction. This is the first report of the density-dependent enhancement of DNA viruses byWolbachia. Further, we report the generation of vpiRNAs in a DNA virus-host interaction for the first time.

scholarly journals Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

2021 ◽  
Vol 22 (9) ◽  
pp. 4438
Author(s):  
Jessica Proulx ◽  
Kathleen Borgmann ◽  
In-Woo Park
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Antiviral Immune Response ◽  
Cellular Processes ◽  
Virus Life Cycle ◽  
Infected Cells ◽  
Dependent Processes

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication.

scholarly journals Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ding ◽  
Jin Wang ◽  
Miaoxin Huang ◽  
Zhangpeng Chen ◽  
Jing Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Knock Out ◽  
Classical Complement Pathway ◽  
Synaptic Remodeling ◽  
The Central Nervous System ◽  
System Activation ◽  
Knock Out Mice ◽  
Synaptic Pruning

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.

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