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Viruses, Vol. 14, Pages 1628: Inhibition of Venezuelan Equine Encephalitis Virus Using Small Interfering RNAs
In this study, novel vsiRNAs that targeted conserved regions in the nonstructural and structural genes of the VEEV genome were designed and evaluated for antiviral activity in mammalian cells in the context of VEEV infection. The data demonstrate that vsiRNAs were able to effectively decrease the infectious virus titer at earlier time points post infection in the context of the attenuated TC-83 strain and the virulent Trinidad Donkey strain, while the inhibition was overcome at later time points. Depletion of Argonaute 2 protein (Ago2), the catalytic component of the RISC complex, negated the inhibitory effect of the vsiRN...
Source: Viruses - July 26, 2022 Category: Virology Authors: Amrita Haikerwal Michael D. Barrera Nishank Bhalla Weidong Zhou Niloufar Boghdeh Carol Anderson Farhang Alem Aarthi Narayanan Tags: Article Source Type: research

Recent advances on therapeutic potentials of gold and silver nanobiomaterials for human viral diseases
Curr Res Chem Biol. 2022;2:100021. doi: 10.1016/j.crchbi.2022.100021. Epub 2022 Feb 1.ABSTRACTViral diseases are prominent among the widely spread infections threatening human well-being. Real-life clinical successes of the few available therapeutics are challenged by pathogenic resistance and suboptimal delivery to target sites. Nanotechnology has aided the design of functionalised and non-functionalised Au and Ag nanobiomaterials through physical, chemical and biological (green synthesis) methods with improved antiviral efficacy and delivery. In this review, innovative designs as well as interesting antiviral activities ...
Source: Herpes - July 11, 2022 Category: Infectious Diseases Authors: Yusuf Oloruntoyin Ayipo Ajibola Abdulahi Bakare Umar Muhammad Badeggi Akeem Adebayo Jimoh Amudat Lawal Mohd Nizam Mordi Source Type: research

Molecules, Vol. 27, Pages 1170: Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
In this study, nanodelivery systems (hybrid polymeric/solid lipid nanoparticles) using cationic lipids (stearylamine, C9 lipid, and dioctadecylamine) and polymers (branched PEI-g-PEG -PEG) were prepared, characterized, and complexed with siRNA. The four developed delivery systems (F1,F2,F3, and F4) were assessed for stability and potential toxicities against CHIKV. In comparison to the other nanodelivery systems, F4 containing stearylamine (Octadecylamine; ODA), with an induced optimum cationic charge of 45.7 mV in the range of 152.1 nm, allowed maximum siRNA complexation, better stability, and higher transfection, with st...
Source: Molecules - February 9, 2022 Category: Chemistry Authors: Manish Kumar Jeengar Mallesh Kurakula Poonam Patil Ashwini More Ramakrishna Sistla Deepti Parashar Tags: Article Source Type: research

Argonaute-CLIP delineates versatile, functional RNAi networks in Aedes aegypti, a major vector of human viruses
Cell Host Microbe. 2021 Mar 29:S1931-3128(21)00132-3. doi: 10.1016/j.chom.2021.03.004. Online ahead of print.ABSTRACTArgonaute (AGO) proteins bind small RNAs to silence complementary RNA transcripts, and they are central to RNA interference (RNAi). RNAi is critical for regulation of gene expression and antiviral defense in Aedes aegypti mosquitoes, which transmit Zika, chikungunya, dengue, and yellow fever viruses. In mosquitoes, AGO1 mediates miRNA interactions, while AGO2 mediates siRNA interactions. We applied AGO-crosslinking immunoprecipitation (AGO-CLIP) for both AGO1 and AGO2, and we developed a universal software p...
Source: Cell Host and Microbe - April 1, 2021 Category: Microbiology Authors: Kathryn Rozen-Gagnon Meigang Gu Joseph M Luna Ji-Dung Luo Soon Yi Sasha Novack Eliana Jacobson Wei Wang Matthew R Paul Troels K H Scheel Thomas Carroll Charles M Rice Source Type: research

Host ESCRT factors are recruited during chikungunya virus infection and are required for the intracellular viral replication cycle Cell Biology
Chikungunya fever is a re-emerging zoonotic disease caused by chikungunya virus (CHIKV), a member of the Alphavirus genus in the Togaviridae family. Only a few studies have reported on the host factors required for intracellular CHIKV trafficking. Here, we conducted an imaging-based siRNA screen to identify human host factors for intracellular trafficking that are involved in CHIKV infection, examined their interactions with CHIKV proteins, and investigated the contributions of these proteins to CHIKV infection. The results of the siRNA screen revealed that host endosomal sorting complexes required for transport (ESCRT) pr...
Source: Journal of Biological Chemistry - June 4, 2020 Category: Chemistry Authors: Shiho Torii, Yasuko Orba, Michihito Sasaki, Koshiro Tabata, Yuji Wada, Michael Carr, Jody Hobson-Peters, Roy A. Hall, Ayato Takada, Takasuke Fukuhara, Yoshiharu Matsuura, William W. Hall, Hirofumi Sawa Tags: Microbiology Source Type: research

Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation
by Simon Dirmeier, Christopher D ächert, Martijn van Hemert, Ali Tas, Natacha S. Ogando, Frank van Kuppeveld, Ralf Bartenschlager, Lars Kaderali, Marco Binder, Niko Beerenwinkel Genetic perturbation screens using RNA interference (RNAi) have been conducted successfully to identify host factors that are essential for the life cycle of bacteria or viruses. So far, most published studies identified host factors primarily for single pathogens. Furthermore, often only a small subset of genes, e.g., genes encoding kinases, have been targeted. Identification of host factors on a pan-pathogen level, i.e., genes that are crucial ...
Source: PLoS Computational Biology - February 9, 2020 Category: Biology Authors: Simon Dirmeier Source Type: research

Chikungunya virus requires cellular chloride channels for efficient genome replication
In this study, we investigated the role of host-cell chloride (Cl-) channels on CHIKV replication.We demonstrate that specific pharmacological Cl- channel inhibitors significantly inhibit CHIKV replication in a dose-dependent manner, suggesting that Cl-channels are pro-viral factors in human cells. Further analysis of the effect of the inhibitors on CHIKV attachment, entry, viral protein expression and replicon replication demonstrated that Cl- channels are specifically required for efficient CHIKV genome replication. This was conserved in mosquito cells, where CHIKV replication and genome copy number was significantly red...
Source: PLoS Neglected Tropical Diseases - September 3, 2019 Category: Tropical Medicine Authors: Marietta M üller Source Type: research

Macropinocytosis Dependent Entry of Chikungunya Virus into Human Muscle Cells
This study shows for the first time, that the infectious entry of CHIKV into human muscle cells is mediated by macropinocytosis. Together, the da ta from this study may pave the way for the development of specific inhibitors that target the entry process of CHIKV into cells.
Source: PLoS Neglected Tropical Diseases - August 25, 2019 Category: Tropical Medicine Authors: Ching Hua, Regina Lee Source Type: research

Viruses, Vol. 11, Pages 540: Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegypti
Failloux Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA). Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical. Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotyp...
Source: Viruses - June 9, 2019 Category: Virology Authors: Yen Chen Sreenu Kohl Failloux Tags: Article Source Type: research

Induction of RNA interference to block Zika virus replication and transmission in the mosquito Aedes aegypti.
This study lays critical groundwork for pursuing ZIKV transmission-blocking strategies that exploit the Ae. aegypti exo-siRNA response for arbovirus suppression in natural populations. PMID: 31103782 [PubMed - as supplied by publisher]
Source: Insect Biochemistry and Molecular Biology - May 15, 2019 Category: Biochemistry Authors: Magalhaes T, Bergren NA, Bennett SL, Borland EM, Hartman DA, Lymperopoulos K, Sayre R, Borlee BR, Campbell CL, Foy BD, Olson KE, Blair CD, Black W, Kading RC Tags: Insect Biochem Mol Biol Source Type: research

Proteomics Profiling of Chikungunya-Infected Aedes albopictus C6/36 Cells Reveal Important Mosquito Cell Factors in Virus Replication
In this study, the CHIKV-infected C6/36 cells with differential cellular proteins expression were profiled using two-dimensional gel electrophoresis (2DE) coupled with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 2DE analysis on CHIKV-infected C6/36 cells has shown 23 mosquito cellular proteins that are differentially regulated, and which are involved diverse biological pathways, such as protein folding and metabolic processes. Among those identified mosquito proteins, spermatogenesis-associated factor, enolase phosphatase e-1 and chaperonin-60kD have been found to...
Source: PLoS Neglected Tropical Diseases - March 4, 2015 Category: Tropical Medicine Authors: Regina Ching Hua Lee et al. Source Type: research

Chikungunya virus nsP3 & nsP4 interacts with HSP-90 to promote virus replication: HSP-90 inhibitors reduce CHIKV infection and inflammation in vivo.
In this study, using biochemical pull-downs, mass-spectrometry, and microscopic imaging techniques, we have identified novel interactions between CHIKV nsP3 or nsP4 proteins with the host stress-pathway chaperone HSP-90 protein. Indeed, silencing of HSP-90 transcripts using siRNA disrupts CHIKV replication in cultured cells. Furthermore, drugs targeting HSP-90, such as commercially available geldanamycin, as well as other specific HSP-90 inhibitor drugs that had been obtained from a purinome mining approach (HS-10 and SNX-2112) showed dramatic reduction in viral titers and reduced inflammation in a CHIKV mouse model of sev...
Source: Antiviral Research - December 31, 2013 Category: Virology Authors: Rathore AP, Haystead T, Das PK, Merits A, Ng ML, Vasudevan SG Tags: Antiviral Res Source Type: research