MicroRNAs (miRNAs) are approximately 21-24 nucleotide RNAs that mediate repression of messenger RNA (mRNA) translation through recognition of specific miRNA binding sites usually located in the 3' non-translated region. Designed to simulate miRNAs, small interfering RNAs represent a powerful genetic approach to potently inhibit gene expression by mediating cleavage of the intended mRNA target. This strategy has been applied successfully to suppress replication of several viruses, including human immunodeficiency virus type 1 (HIV-1). However, recent evidences indicate that viral RNAs may themselves be processed, to some extent, by the endogenous miRNA biosynthetic machinery in mammalian cells, extending previous observations in plants. The resulting viral miRNAs may exert regulatory effects towards host and/or viral genes that may influence viral replication and modulate the course of infection. Viral miRNA generation and/or action may be limited by counteraction through inhibitory viral RNAs and/or proteins. This review article will focus on the relationship between HIV-1 and miRNA-guided RNA silencing, and discuss the different aspects of their interaction. As we learn more about the mechanism and importance of small RNA-based antiviral systems, a more intricate picture of the interaction between HIV-1 and a proven antiviral defense mechanism in lower eukaryotes is emerging.
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http://dx.doi.org/10.1016/j.virusres.2006.06.015 | DOI Listing |
PLoS Biol
January 2025
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
RNA interference (RNAi) mediates antiviral defense in many eukaryotes. Caenorhabditis elegans mutants that disable RNAi are more sensitive to viral infection. Many mutants that enhance RNAi have also been identified; these mutations may reveal genes that are normally down-regulated in antiviral defense.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
Achieving targeted hypermutation of specific genomic sequences without affecting other regions remains a key challenge in continuous evolution. To address this, we evolved a T7 RNA polymerase (RNAP) mutant that synthesizes single-stranded DNA (ssDNA) instead of RNA in vivo, while still exclusively recognizing the T7 promoter. By increasing the error rate of the T7 RNAP mutant, it generates mutated ssDNA that recombines with homologous sequences in the genome, leading to targeted genomic hypermutation.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
The heterotrimeric RNA-dependent RNA polymerase (RdRp) of influenza A virus catalyzes viral RNA transcription (vRNA→mRNA) and replication (vRNA→cRNA→vRNA) by adopting different conformations. A switch from transcription to replication occurs at a relatively late stage of infection. We recently reported that the viral NS2 protein, expressed at later stages from a spliced transcript of the NS segment messenger RNA (mRNA), inhibits transcription, promotes replication and plays a key role in the transcription-to-replication switch.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Single-Molecule and Cell Mechanobiology Laboratory, Daejeon, 34141, South Korea.
Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as a nucleic acid motor that unwinds its ds substrates or as a chaperone that alters the stability of its substrates, but the two activities have not yet been reported to act simultaneously. Here, we used single-molecule techniques to unravel the synergistic coordination of helicase and chaperone activities, and found that the severe acute respiratory syndrome coronavirus helicase (nsp13) is capable of two modes of action: (i) binding of nsp13 in tandem with the fork junction of the substrate mechanically unwinds the substrate by an ATP-driven synchronous power stroke; and (ii) free nsp13, which is not bound to the substrate but complexed with ADP in solution, destabilizes the substrate through collisions between transient binding and unbinding events with unprecedented melting capability.
View Article and Find Full Text PDFMikrobiyol Bul
January 2025
Kocaeli Üniversitesi Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, Kocaeli.
Son yıllarda pandemi nedeniyle virüslerin tanı ve tedavisine yönelik terapötik yöntemlerin geliştirilmesi ve antivirallerin test edilmesi amacıyla çok sayıda in vitro çalışma yapılmaktadır. Literatürde SARS-CoV-2'nin modellenebilmesi için HCoV-229E'nin kullanımının güvenli ve yeterli olup olmadığını inceleyen çalışmalar sınırlıdır. Bu sebeple bu çalışmada, BSL-2 şartlarında gerçekleştirilebilen HCoV-229E kültürü ve kantitasyon çalışmalarının, BSL-3 şartları gerektiren SARS-CoV-2 deneylerinde bir ön çalışma modeli olup olamayacağının antiviral etkinlik analizleri üzerinden araştırılması amaçlanmıştır.
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