scholarly journals The Capsid Protein of Rubella Virus Antagonizes RNA Interference in Mammalian Cells

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 154
Author(s):  
Jiuyue Xu ◽  
Jing Kong ◽  
Bao Lyu ◽  
Xiaotong Wang ◽  
Qi Qian ◽  
...  
Keyword(s):  
Rna Interference ◽  
Capsid Protein ◽  
Rubella Virus ◽  
Mammalian Cells ◽  
Defense Mechanism ◽  
Ectopic Expression ◽  
Infectious Agent ◽  
Binding Activity ◽  
Health Concern ◽  
Rnai Response

Rubella virus (RuV) is the infectious agent of a series of birth defect diseases termed congenital rubella syndrome, which is a major public health concern all around the world. RNA interference (RNAi) is a crucial antiviral defense mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi response. However, there is little knowledge about whether and how RuV antagonizes RNAi. In this study, we identified that the RuV capsid protein is a potent VSR that can efficiently suppress shRNA- and siRNA-induced RNAi in mammalian cells. Moreover, the VSR activity of the RuV capsid is dependent on its dimerization and double-stranded RNA (dsRNA)-binding activity. In addition, ectopic expression of the RuV capsid can effectively rescue the replication defect of a VSR-deficient virus or replicon, implying that the RuV capsid can act as a VSR in the context of viral infection. Together, our findings uncover that RuV encodes a VSR to evade antiviral RNAi response, which expands our understanding of RuV–host interaction and sheds light on the potential therapeutic target against RuV.

scholarly journals The Capsid Protein of Semliki Forest Virus Antagonizes RNA Interference in Mammalian Cells

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Qi Qian ◽  
Hui Zhou ◽  
Ting Shu ◽  
Jingfang Mu ◽  
Yuan Fang ◽  
...  
Keyword(s):  
Rna Interference ◽  
Capsid Protein ◽  
Mammalian Cells ◽  
Semliki Forest Virus ◽  
Rna Viruses ◽  
Strong Support ◽  
Life Cycles ◽  
Immune Defense ◽  
Rnai Pathway ◽  
Viral Suppressors

ABSTRACT RNA interference (RNAi) is a conserved antiviral immune defense in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs) to counteract antiviral RNAi. Alphaviruses are a large group of positive-stranded RNA viruses that maintain their transmission and life cycles in both mosquitoes and mammals. However, there is little knowledge about how alphaviruses antagonize RNAi in both host organisms. In this study, we identified that Semliki Forest virus (SFV) capsid protein can efficiently suppress RNAi in both insect and mammalian cells by sequestrating double-stranded RNA and small interfering RNA. More importantly, when the VSR activity of SFV capsid was inactivated by reverse genetics, the resulting VSR-deficient SFV mutant showed severe replication defects in mammalian cells, which could be rescued by blocking the RNAi pathway. Besides, capsid protein of Sindbis virus also inhibited RNAi in cells. Together, our findings show that SFV uses capsid protein as VSR to antagonize RNAi in infected mammalian cells, and this mechanism is probably used by other alphaviruses, which shed new light on the knowledge of SFV and alphavirus. IMPORTANCE Alphaviruses are a genus of positive-stranded RNA viruses and include numerous important human pathogens, such as Chikungunya virus, Ross River virus, Western equine encephalitis virus, etc., which create the emerging and reemerging public health threat worldwide. RNA interference (RNAi) is one of the most important antiviral mechanisms in plants and insects. Accumulating evidence has provided strong support for the existence of antiviral RNAi in mammals. In response to antiviral RNAi, viruses have evolved to encode viral suppressors of RNAi (VSRs) to antagonize the RNAi pathway. It is unclear whether alphaviruses encode VSRs that can suppress antiviral RNAi during their infection in mammals. In this study, we first uncovered that capsid protein encoded by Semliki Forest virus (SFV), a prototypic alphavirus, had a potent VSR activity that can antagonize antiviral RNAi in the context of SFV infection in mammalian cells, and this mechanism is probably used by other alphaviruses.

scholarly journals The Baculovirus Antiapoptotic p35 Protein Functions as an Inhibitor of the Host RNA Interference Antiviral Response

2015 ◽  
Vol 89 (16) ◽  
pp. 8182-8192 ◽  
Author(s):  
Mohammad Mehrabadi ◽  
Mazhar Hussain ◽  
Leila Matindoost ◽  
Sassan Asgari
Keyword(s):  
Rna Interference ◽  
Mammalian Cells ◽  
Microbial Control ◽  
Rnai Pathway ◽  
Inhibitor Of Apoptosis ◽  
Virus Infections ◽  
Content Type ◽  
Protein Functions ◽  
Dsrna Cleavage ◽  
Rnai Response

ABSTRACTRNA interference (RNAi) is considered an ancient antiviral defense in diverse organisms, including insects. Virus infections generate double-strand RNAs (dsRNAs) that trigger the RNAi machinery to process dsRNAs into virus-derived short interfering RNAs (vsiRNAs), which target virus genomes, mRNAs, or replication intermediates. Viruses, in turn, have evolved viral suppressors of RNAi (VSRs) to counter host antiviral RNAi. Following recent discoveries that insects mount an RNAi response against DNA viruses, in this study, we found thatAutographa californicamultiple nucleopolyhedrovirus (AcMNPV) infection similarly induces an RNAi response inSpodoptera frugiperdacells by generating a large number of vsiRNAs postinfection. Interestingly, we found that AcMNPV expresses a potent VSR to counter RNAi. The viralp35gene, which is well known as an inhibitor of apoptosis, was found to be responsible for the suppression of RNAi in diverse insect and mammalian cells. The VSR activity of p35 was further confirmed by ap35-null AcMNPV that did not suppress the response. In addition, our results showed that the VSR activity is not due to inhibition of dsRNA cleavage by Dicer-2 but acts downstream in the RNAi pathway. Furthermore, we found that the VSR activity is not linked to the antiapoptotic activity of the protein. Overall, our results provide evidence for the existence of VSR activity in a double-stranded DNA virus and identify the responsible gene, which is involved in the inhibition of RNAi as well as apoptosis.IMPORTANCEOur findings demonstrate the occurrence of an insect RNAi response against a baculovirus (AcMNPV) that is highly utilized in microbial control, biological and biomedical research, and protein expression. Moreover, our investigations led to the identification of a viral suppressor of RNAi activity and the gene responsible for the activity. Notably, this gene is also a potent inhibitor of apoptosis. The outcomes signify the dual role of a virus-encoded protein in nullifying two key antiviral responses, apoptosis and RNAi.

scholarly journals Antiviral Effects of Anthocyanins and Phytochemicals as Natural Dietary Compounds on Different Virus Sources

2020 ◽  
Vol 8 (3) ◽  
pp. 674-681
Author(s):  
Dhriti Choudhary ◽  
Min-Hsiung Pan
Keyword(s):  
Defense Mechanism ◽  
Viral Infections ◽  
Health Benefit ◽  
Infectious Agent ◽  
Health Concern ◽  
Virus Infections ◽  
Life Threatening ◽  
Antiviral Activities ◽  
Anti Oxidant ◽  
Anti Fungal

Virus, an infectious agent is the main reason causing the deaths by life-threatening diseases, including HIV, cancer, influenza, herpes, dengue, hepatitis, chikungunya all around the world. Virus infections are a global health concern, due to worldwide travel and gradual modernization, the viral eruption is an epidemic menace and can be avoided by minimizing publicity to infectious viruses. Even with so many precautions, viral diseases can still spread and cause great risk to human health and requires proper sanitation by disinfectants or anti-viral agents. Very few vaccines are available that can effectively treat viral infections. As there are many advances progressing in the health care sector, there are some efficient anti-viral treatments and therapies, still some virus does not have effective vaccinations and therapies yet. For the past few years, there has been an intensive effort to study the defense mechanism of natural products such as foods and drinks we normally consume in our day-to-day life that may inhibit some anti-viral activities and some advantages over synthetic vaccines. The development of natural vaccines, that work against the virus is still a major goal. As it has been identified that the natural dietary compounds such as phytochemicals, anthocyanins, flavonoids, curcumins, polyphenols, and many more have some health benefit properties which may include anti-inflammation, anti-oxidant, anti-bacterial, anti-cancer, anti-viral, anti-fungal activities. This mini-review generally summarizes the antiviral activities of anthocyanins and phytochemicals from various natural plant sources on different virus origins.

scholarly journals Analyses of Phosphorylation Events in the Rubella Virus Capsid Protein: Role in Early Replication Events

2006 ◽  
Vol 80 (14) ◽  
pp. 6917-6925 ◽  
Author(s):  
LokMan J. Law ◽  
Carolina S. Ilkow ◽  
Wen-Pin Tzeng ◽  
Matthew Rawluk ◽  
David T. Stuart ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Rubella Virus ◽  
Rna Binding ◽  
Virus Assembly ◽  
Binding Activity ◽  
Amino Acid Residues ◽  
Direct Role ◽  
Virus Capsid ◽  
Early Replication ◽  
Virus Capsid Protein

ABSTRACT The Rubella virus capsid protein is phosphorylated prior to virus assembly. Our previous data are consistent with a model in which dynamic phosphorylation of the capsid regulates its RNA binding activity and, in turn, nucleocapsid assembly. In the present study, the process of capsid phosphorylation was examined in further detail. We show that phosphorylation of serine 46 in the RNA binding region of the capsid is required to trigger phosphorylation of additional amino acid residues that include threonine 47. This residue likely plays a direct role in regulating the binding of genomic RNA to the capsid. We also provide evidence which suggests that the capsid is dephosphorylated prior to or during virus budding. Finally, whereas the phosphorylation state of the capsid does not directly influence the rate of synthesis of viral RNA and proteins or the assembly and secretion of virions, the presence of phosphate on the capsid is critical for early events in virus replication, most likely the uncoating of virions and/or disassembly of nucleocapsids.

scholarly journals Analysis of maxillopedia Expression Pattern and Larval Cuticular Phenotype in Wild-Type and Mutant Tribolium

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 721-731 ◽  
Author(s):  
Teresa D Shippy ◽  
Jianhua Guo ◽  
Susan J Brown ◽  
Richard W Beeman ◽  
Robin E Denell
Keyword(s):  
Rna Interference ◽  
Expression Pattern ◽  
Tribolium Castaneum ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Homeotic Gene ◽  
Wild Type ◽  
Double Stranded Rna ◽  
Similar Expression ◽  
Mutant Phenotypes

Abstract The Tribolium castaneum homeotic gene maxillopedia (mxp) is the ortholog of Drosophila proboscipedia (pb). Here we describe and classify available mxp alleles. Larvae lacking all mxp function die soon after hatching, exhibiting strong transformations of maxillary and labial palps to legs. Hypomorphic mxp alleles produce less severe transformations to leg. RNA interference with maxillopedia double-stranded RNA results in phenocopies of mxp mutant phenotypes ranging from partial to complete transformations. A number of gain-of-function (GOF) mxp alleles have been isolated based on transformations of adult antennae and/or legs toward palps. Finally, we have characterized the mxp expression pattern in wild-type and mutant embryos. In normal embryos, mxp is expressed in the maxillary and labial segments, whereas ectopic expression is observed in some GOF variants. Although mxp and Pb display very similar expression patterns, pb null embryos develop normally. The mxp mutant larval phenotype in Tribolium is consistent with the hypothesis that an ancestral pb-like gene had an embryonic function that was lost in the lineage leading to Drosophila.

scholarly journals Drosophila Mi-2 Negatively Regulates dDREF by Inhibiting Its DNA-Binding Activity

2002 ◽  
Vol 22 (14) ◽  
pp. 5182-5193 ◽  
Author(s):  
Fumiko Hirose ◽  
Nobuko Ohshima ◽  
Eun-Jeong Kwon ◽  
Hideki Yoshida ◽  
Masamitsu Yamaguchi
Keyword(s):  
Dna Binding ◽  
Polytene Chromosomes ◽  
Ectopic Expression ◽  
Binding Activity ◽  
Mobility Shift ◽  
Interacting Protein ◽  
Reciprocal Regulation ◽  
Dna Binding Activity ◽  
Expression Of Genes ◽  
Biochemical Analyses

ABSTRACT Drosophila melanogaster DNA replication-related element (DRE) factor (dDREF) is a transcriptional regulatory factor required for the expression of genes carrying the 5′-TATCGATA DRE. dDREF has been reported to bind to a sequence in the chromatin boundary element, and thus, dDREF may play a part in regulating insulator activity. To generate further insights into dDREF function, we carried out a Saccharomyces cerevisiae two-hybrid screening with DREF polypeptide as bait and identified Mi-2 as a DREF-interacting protein. Biochemical analyses revealed that the C-terminal region of Drosophila Mi-2 (dMi-2) specifically binds to the DNA-binding domain of dDREF. Electrophoretic mobility shift assays showed that dMi-2 thereby inhibits the DNA-binding activity of dDREF. Ectopic expression of dDREF and dMi-2 in eye imaginal discs resulted in severe and mild rough-eye phenotypes, respectively, whereas flies simultaneously expressing both proteins exhibited almost-normal eye phenotypes. Half-dose reduction of the dMi-2 gene enhanced the DREF-induced rough-eye phenotype. Immunostaining of polytene chromosomes of salivary glands showed that dDREF and dMi-2 bind in mutually exclusive ways. These lines of evidence define a novel function of dMi-2 in the negative regulation of dDREF by its DNA-binding activity. Finally, we postulated that dDREF and dMi-2 may demonstrate reciprocal regulation of their functions.

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