Video Experimental Relacionado
Updated: Jun 12, 2026
09:31
Fluorescence-based Neuraminidase Inhibition Assay to Assess the Susceptibility of Influenza Viruses to The Neuraminidase Inhibitor Class of Antivirals
Published on: April 15, 2017
Las mutaciones secundarias permisivas permiten la evolución de la resistencia a oseltamivir para la influenza
Jesse D Bloom1, Lizhi Ian Gong, David Baltimore
1Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Science (New York, N.Y.)
|June 5, 2010
Resumen
La mutación His274-->Tyr274 confiere resistencia al oseltamivir en los virus de la influenza. Las mutaciones secundarias permitieron que esta cepa resistente se convirtiera en dominante al restaurar la aptitud viral.
Área de la Ciencia:
- Virología Virología.
- La resistencia a los antimicrobianos se ha desarrollado.
Sus antecedentes:
- La mutación His274-->Tyr274 (H274Y) en la neuraminidasa de la influenza N1 confiere resistencia al oseltamivir.
- Anteriormente se creía que esta mutación reducía la aptitud viral, impidiendo su propagación.
Objetivo del estudio:
- Investigar los mecanismos detrás del rápido predominio de los virus de la gripe H1N1 estacionales que contienen H274Y a partir de 2007-2008.
- Para entender cómo se restaura la aptitud viral en presencia de la mutación H274Y.
Principales métodos:
- Análisis de los niveles de neuraminidasa en la superficie celular en relación con la mutación H274Y.
- Identificación de mutaciones secundarias que compensan el defecto de aptitud causado por H274Y.
Principales resultados:
- La mutación H274Y reduce la cantidad de neuraminidasa que llega a la superficie celular.
- Se identificaron mutaciones secundarias que contrarrestan este defecto y restauran la aptitud viral.
- Estas mutaciones permisivas precedieron a la aparición generalizada de H274Y en aislamientos estacionales de H1N1.
Conclusiones:
- La evolución de la resistencia al oseltamivir fue facilitada por mutaciones permisivas preexistentes que permitieron la tolerancia de la mutación H274Y.
- Comprender esta vía evolutiva puede ayudar a predecir el futuro desarrollo de resistencia al oseltamivir en otras cepas de influenza.
Videos de Conceptos Relacionados
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
02:28Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
01:25Inhibitors Of Virion Release
Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
01:18Mutations in Microorganisms
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
01:25Mechanism of Antibiotic Resistance in MRSA
Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
01:30Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).