Molecular basis of live-attenuated influenza virus.
Identifieur interne : 000864 ( Main/Exploration ); précédent : 000863; suivant : 000865Molecular basis of live-attenuated influenza virus.
Auteurs : Wen He [République populaire de Chine] ; Wei Wang ; Huamin Han ; Lei Wang ; Ge Zhang ; Bin GaoSource :
- PloS one [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- ARN viral (génétique), Animaux, Grippe humaine (), Grippe humaine (virologie), Humains, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (virologie), Lignée cellulaire, Mutation, Protéines virales (génétique), RNA replicase (génétique), Régulation de l'expression des gènes viraux, Souris, Souris de lignée C57BL, Sous-type H1N1 du virus de la grippe A (génétique), Sous-type H1N1 du virus de la grippe A (physiologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (usage thérapeutique), Vaccins atténués (génétique), Vaccins atténués (usage thérapeutique).
- MESH :
- génétique : ARN viral, Protéines virales, RNA replicase, Sous-type H1N1 du virus de la grippe A, Vaccins antigrippaux, Vaccins atténués.
- physiologie : Sous-type H1N1 du virus de la grippe A.
- usage thérapeutique : Vaccins antigrippaux, Vaccins atténués.
- virologie : Grippe humaine, Infections à Orthomyxoviridae.
- Animaux, Grippe humaine, Humains, Infections à Orthomyxoviridae, Lignée cellulaire, Mutation, Régulation de l'expression des gènes viraux, Souris, Souris de lignée C57BL.
English descriptors
- KwdEn :
- Animals, Cell Line, Gene Expression Regulation, Viral, Humans, Influenza A Virus, H1N1 Subtype (genetics), Influenza A Virus, H1N1 Subtype (physiology), Influenza Vaccines (genetics), Influenza Vaccines (therapeutic use), Influenza, Human (prevention & control), Influenza, Human (virology), Mice, Mice, Inbred C57BL, Mutation, Orthomyxoviridae Infections (prevention & control), Orthomyxoviridae Infections (virology), RNA Replicase (genetics), RNA, Viral (genetics), Vaccines, Attenuated (genetics), Vaccines, Attenuated (therapeutic use), Viral Proteins (genetics).
- MESH :
- chemical , genetics : Influenza Vaccines, RNA Replicase, RNA, Viral, Vaccines, Attenuated, Viral Proteins.
- genetics : Influenza A Virus, H1N1 Subtype.
- physiology : Influenza A Virus, H1N1 Subtype.
- prevention & control : Influenza, Human, Orthomyxoviridae Infections.
- chemical , therapeutic use : Influenza Vaccines, Vaccines, Attenuated.
- virology : Influenza, Human, Orthomyxoviridae Infections.
- Animals, Cell Line, Gene Expression Regulation, Viral, Humans, Mice, Mice, Inbred C57BL, Mutation.
Abstract
Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular) response that represents a naturally occurring transient infection. The cold-adapted (ca) influenza A/AA/6/60 (H2N2) (AA ca) virus is the backbone for the live attenuated trivalent seasonal influenza vaccine licensed in the United States. Similarly, the influenza A components of live-attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47) along with virulent epidemic strains. However, the mechanism of temperature-sensitive attenuation is largely elusive. To understand how modification at genetic level of influenza virus would result in attenuation of human influenza virus A/PR/8/34 (H1N1,A/PR8), we investigated the involvement of key mutations in the PB1 and/or PB2 genes in attenuation of influenza virus in vitro and in vivo. We have demonstrated that a few of residues in PB1 and PB2 are critical for the phenotypes of live attenuated, temperature sensitive influenza viruses by minigenome assay and real-time PCR. The information of these mutation loci could be used for elucidation of mechanism of temperature-sensitive attenuation and as a new strategy for influenza vaccine development.
DOI: 10.1371/journal.pone.0060413
PubMed: 23555969
Affiliations:
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Le document en format XML
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<term>Gene Expression Regulation, Viral</term>
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<term>Influenza A Virus, H1N1 Subtype (physiology)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (therapeutic use)</term>
<term>Influenza, Human (prevention & control)</term>
<term>Influenza, Human (virology)</term>
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<term>Orthomyxoviridae Infections (virology)</term>
<term>RNA Replicase (genetics)</term>
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<term>Vaccines, Attenuated (therapeutic use)</term>
<term>Viral Proteins (genetics)</term>
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<term>Animaux</term>
<term>Grippe humaine ()</term>
<term>Grippe humaine (virologie)</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Infections à Orthomyxoviridae (virologie)</term>
<term>Lignée cellulaire</term>
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<term>Vaccins atténués (usage thérapeutique)</term>
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<front><div type="abstract" xml:lang="en">Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular) response that represents a naturally occurring transient infection. The cold-adapted (ca) influenza A/AA/6/60 (H2N2) (AA ca) virus is the backbone for the live attenuated trivalent seasonal influenza vaccine licensed in the United States. Similarly, the influenza A components of live-attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47) along with virulent epidemic strains. However, the mechanism of temperature-sensitive attenuation is largely elusive. To understand how modification at genetic level of influenza virus would result in attenuation of human influenza virus A/PR/8/34 (H1N1,A/PR8), we investigated the involvement of key mutations in the PB1 and/or PB2 genes in attenuation of influenza virus in vitro and in vivo. We have demonstrated that a few of residues in PB1 and PB2 are critical for the phenotypes of live attenuated, temperature sensitive influenza viruses by minigenome assay and real-time PCR. The information of these mutation loci could be used for elucidation of mechanism of temperature-sensitive attenuation and as a new strategy for influenza vaccine development.</div>
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