A study of the virulence in mice of high copying fidelity variants of human enterovirus 71
•Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of HEV71.•Mouse-adapted HEV71 strains were constructed to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus.•S264L and S264L-G64R were attenuated compared...
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| Veröffentlicht in: | Virus research 2013-09, Vol.176 (1-2), p.265-272 |
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| creator | Sadeghipour, Sara McMinn, Peter C. |
| description | •Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of HEV71.•Mouse-adapted HEV71 strains were constructed to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus.•S264L and S264L-G64R were attenuated compared to G64R and parental virus.•Parental virus and G64R infection induced severe generalised necrotising myositis.•S264L and S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis.
Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model. |
| doi_str_mv | 10.1016/j.virusres.2013.06.019 |
| format | Article |
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Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model.</description><identifier>ISSN: 0168-1702</identifier><identifier>EISSN: 1872-7492</identifier><identifier>DOI: 10.1016/j.virusres.2013.06.019</identifier><identifier>PMID: 23856384</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Amino Acid Substitution ; animal models ; Animal Structures - pathology ; Animals ; Disease Models, Animal ; DNA Mutational Analysis ; Enterovirus A ; Enterovirus A, Human - genetics ; Enterovirus A, Human - pathogenicity ; Enterovirus C ; Enterovirus Infections - pathology ; Enterovirus Infections - virology ; Human enterovirus 71 ; Mice ; Mice, Inbred BALB C ; Mutant Proteins - genetics ; Mutant Proteins - metabolism ; mutation ; Mutation, Missense ; myositis ; phenotype ; replication ; RNA Replicase - genetics ; RNA Replicase - metabolism ; skeletal muscle ; Survival Analysis ; Virulence ; viruses</subject><ispartof>Virus research, 2013-09, Vol.176 (1-2), p.265-272</ispartof><rights>2013 Elsevier B.V.</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved.</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved. 2013 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-120ded63fb69497db3eb74d9dbd88b633277eaea2c0d7b678da3a7ae92c1e4e13</citedby><cites>FETCH-LOGICAL-c594t-120ded63fb69497db3eb74d9dbd88b633277eaea2c0d7b678da3a7ae92c1e4e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.virusres.2013.06.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27925,27926,45996</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23856384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sadeghipour, Sara</creatorcontrib><creatorcontrib>McMinn, Peter C.</creatorcontrib><title>A study of the virulence in mice of high copying fidelity variants of human enterovirus 71</title><title>Virus research</title><addtitle>Virus Res</addtitle><description>•Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of HEV71.•Mouse-adapted HEV71 strains were constructed to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus.•S264L and S264L-G64R were attenuated compared to G64R and parental virus.•Parental virus and G64R infection induced severe generalised necrotising myositis.•S264L and S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis.
Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model.</description><subject>Amino Acid Substitution</subject><subject>animal models</subject><subject>Animal Structures - pathology</subject><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>DNA Mutational Analysis</subject><subject>Enterovirus A</subject><subject>Enterovirus A, Human - genetics</subject><subject>Enterovirus A, Human - pathogenicity</subject><subject>Enterovirus C</subject><subject>Enterovirus Infections - pathology</subject><subject>Enterovirus Infections - virology</subject><subject>Human enterovirus 71</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mutant Proteins - genetics</subject><subject>Mutant Proteins - metabolism</subject><subject>mutation</subject><subject>Mutation, Missense</subject><subject>myositis</subject><subject>phenotype</subject><subject>replication</subject><subject>RNA Replicase - genetics</subject><subject>RNA Replicase - metabolism</subject><subject>skeletal muscle</subject><subject>Survival Analysis</subject><subject>Virulence</subject><subject>viruses</subject><issn>0168-1702</issn><issn>1872-7492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1v2zAQhomiReOm_Qspxy5S-WWSWooGQb-AAB2SLF0IijzZNCTRJSUD_vel4iRopkw33HPvHe5B6IKSmhIqP-_qQ0hzTpBrRiiviawJbV6hFdWKVUo07DVaFVBXVBF2ht7lvCOESK7kW3TGuF5LrsUK_bnEeZr9EccOT1vAS2oPowMcRjyEUktjGzZb7OL-GMYN7oKHPkxHfLAp2HHK98Q82BHDOEGK94dhRd-jN53tM3x4qOfo7vu326uf1fXvH7-uLq8rt27EVFFGPHjJu1Y2olG-5dAq4Rvfeq1byTlTCixY5ohXrVTaW26VhYY5CgIoP0dfTrn7uR3Au3JFsr3ZpzDYdDTRBvO8M4at2cSDUZQKIXUJ-PQQkOLfGfJkhpAd9L0dIc7ZUCkFbYRYrwsqT6hLMZfvd09rKDGLGLMzj2LMIsYQaYqYMnjx_5FPY48mCvDxBHQ2GrtJIZu7m5IgizXWaLLs_noioDzzECCZ7MKiyocEbjI-hpeu-AfmY66_</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Sadeghipour, Sara</creator><creator>McMinn, Peter C.</creator><general>Elsevier B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20130901</creationdate><title>A study of the virulence in mice of high copying fidelity variants of human enterovirus 71</title><author>Sadeghipour, Sara ; McMinn, Peter C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-120ded63fb69497db3eb74d9dbd88b633277eaea2c0d7b678da3a7ae92c1e4e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Substitution</topic><topic>animal models</topic><topic>Animal Structures - pathology</topic><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>DNA Mutational Analysis</topic><topic>Enterovirus A</topic><topic>Enterovirus A, Human - genetics</topic><topic>Enterovirus A, Human - pathogenicity</topic><topic>Enterovirus C</topic><topic>Enterovirus Infections - pathology</topic><topic>Enterovirus Infections - virology</topic><topic>Human enterovirus 71</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mutant Proteins - genetics</topic><topic>Mutant Proteins - metabolism</topic><topic>mutation</topic><topic>Mutation, Missense</topic><topic>myositis</topic><topic>phenotype</topic><topic>replication</topic><topic>RNA Replicase - genetics</topic><topic>RNA Replicase - metabolism</topic><topic>skeletal muscle</topic><topic>Survival Analysis</topic><topic>Virulence</topic><topic>viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sadeghipour, Sara</creatorcontrib><creatorcontrib>McMinn, Peter C.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Virus research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sadeghipour, Sara</au><au>McMinn, Peter C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A study of the virulence in mice of high copying fidelity variants of human enterovirus 71</atitle><jtitle>Virus research</jtitle><addtitle>Virus Res</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>176</volume><issue>1-2</issue><spage>265</spage><epage>272</epage><pages>265-272</pages><issn>0168-1702</issn><eissn>1872-7492</eissn><abstract>•Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of HEV71.•Mouse-adapted HEV71 strains were constructed to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus.•S264L and S264L-G64R were attenuated compared to G64R and parental virus.•Parental virus and G64R infection induced severe generalised necrotising myositis.•S264L and S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis.
Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>23856384</pmid><doi>10.1016/j.virusres.2013.06.019</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Substitution animal models Animal Structures - pathology Animals Disease Models, Animal DNA Mutational Analysis Enterovirus A Enterovirus A, Human - genetics Enterovirus A, Human - pathogenicity Enterovirus C Enterovirus Infections - pathology Enterovirus Infections - virology Human enterovirus 71 Mice Mice, Inbred BALB C Mutant Proteins - genetics Mutant Proteins - metabolism mutation Mutation, Missense myositis phenotype replication RNA Replicase - genetics RNA Replicase - metabolism skeletal muscle Survival Analysis Virulence viruses |
| title | A study of the virulence in mice of high copying fidelity variants of human enterovirus 71 |
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