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Retrovirus population diversity within infected hosts is commonly high due in part to elevated rates of replication, mutation, and recombination. This high genetic diversity often complicates the development of effective diagnostics, vaccines, and antiviral drugs. This review highlights the diverse vectors and approaches that have been used to examine mutation and recombination in retroviruses. Retroviral vectors for these purposes can broadly be divided into two categories: those that utilize reporter genes as mutation or recombination targets and those that utilize viral genes as targets of mutation or recombination. Reporter gene vectors greatly facilitate the detection, quantification, and characterization of mutants and/or recombinants, but may not fully recapitulate the patterns of mutagenesis or recombination observed in native viral gene sequences. In contrast, the detection of mutations or recombination events directly in viral genes is more biologically relevant but also typically more challenging and inefficient. We will highlight the advantages and disadvantages of the various vectors and approaches used as well as propose ways in which they could be improved.
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http://dx.doi.org/10.3390/v6093612 | DOI Listing |
PLoS Pathog
September 2025
Institut de Chimie des Substances Naturelles, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France.
Respiratory syncytial virus (RSV), the most common cause of bronchiolitis and pneumonia in infants, elicits a remarkably weak innate immune response. This is partly due to type I interferon (IFN) antagonism by the non-structural RSV NS1 protein. It was recently suggested that NS1 could modulate host transcription via an interaction with the MED25 subunit of the Mediator complex.
View Article and Find Full Text PDFJ Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
View Article and Find Full Text PDFMicrobiol Spectr
September 2025
Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Efficient DNA delivery is essential for genetic manipulation of mycobacteria and for dissecting their physiology, pathogenesis, and drug resistance. Although electroporation enables transformation efficiencies exceeding 10⁵ CFU per µg DNA in and , it remains highly inefficient in many nontuberculous mycobacteria (NTM), including . Here, we discovered that NTM such as exhibit exceptional tolerance to ultra-high electric field strengths and that hypertonic preconditioning partially protects cells from electroporation-induced damage.
View Article and Find Full Text PDFFront Cell Infect Microbiol
September 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang-An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, China.
infections represent a significant public health concern. Despite their clinical relevance, the genetic determinants underlying bacterial fitness and virulence remain incompletely characterized. In this study, we systematically identified genes involved in host adaptation by generating a transposon mutant library and integrating a infection model with transposon sequencing (Tn-seq) technology.
View Article and Find Full Text PDFFront Immunol
September 2025
Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata IDI-IRCCS, Rome, Italy.
Background: Sézary syndrome (SS) is an aggressive and leukemic variant of Cutaneous T-cell Lymphoma (CTCL) with an incidence of 1 case per million people per year. It is characterized by a complex and heterogeneous profile of genetic alteration ns that has so far precluded the development of a specific and definitive therapeutic intervention.
Methods: Deep-RNA-sequencing (RNA-seq) data were used to analyze the single nucleotide variants (SNVs) carried by 128 putative CTCL-driver genes, previously identified as mutated in genomic studies, in longitudinal SS samples collected from 17 patients subjected to extracorporeal photopheresis (ECP) with Interferon-α.