Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71
Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis....
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Veröffentlicht in: | Vaccine 2008-02, Vol.26 (7), p.891-898 |
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creator | Chen, Hsiao-Ling Wang, Li-Chung Chang, Chi-Hsuan Yen, Chih-Ching Cheng, Winston T.K Wu, Shinn-Chih Hung, Che-Ming Kuo, Meng-Fu Chen, Chuan-Mu |
description | Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF. |
doi_str_mv | 10.1016/j.vaccine.2007.12.013 |
format | Article |
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Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2007.12.013</identifier><identifier>PMID: 18207613</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animal models ; Animals ; Animals, Newborn ; Antimicrobial agents ; Antiviral activity ; Antiviral Agents - immunology ; Antiviral Agents - metabolism ; Biological and medical sciences ; Body Weight ; Child, Preschool ; Cytomegalovirus ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Enterovirus ; Enterovirus - isolation & purification ; Enterovirus - pathogenicity ; Enterovirus 71 ; Enterovirus Infections - mortality ; Enterovirus Infections - prevention & control ; Enterovirus Infections - virology ; Female ; Females ; Fundamental and applied biological sciences. Psychology ; HIV ; Human immunodeficiency virus ; Humans ; Infant, Newborn ; Infections ; Lactalbumin - genetics ; Lactalbumin - immunology ; Lactalbumin - metabolism ; Lactation ; Lactoferrin - genetics ; Lactoferrin - immunology ; Lactoferrin - metabolism ; Mammals ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Microbiology ; Milk ; Milk - chemistry ; Milk - metabolism ; Miscellaneous ; Mortality ; Neonatal viral infection ; Porcine lactoferrin ; Recombinant Proteins - genetics ; Recombinant Proteins - immunology ; Recombinant Proteins - metabolism ; Rodents ; Survival ; Swine ; Transgenic animals ; Transgenic mice ; Virology ; Yeast</subject><ispartof>Vaccine, 2008-02, Vol.26 (7), p.891-898</ispartof><rights>Elsevier Ltd</rights><rights>2007 Elsevier Ltd</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Elsevier Limited Feb 13, 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-73e00412ffbc892efa2815254a9777dc527463377b91ae7a1d45f42be251881f3</citedby><cites>FETCH-LOGICAL-c507t-73e00412ffbc892efa2815254a9777dc527463377b91ae7a1d45f42be251881f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1558808763?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20043503$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18207613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hsiao-Ling</creatorcontrib><creatorcontrib>Wang, Li-Chung</creatorcontrib><creatorcontrib>Chang, Chi-Hsuan</creatorcontrib><creatorcontrib>Yen, Chih-Ching</creatorcontrib><creatorcontrib>Cheng, Winston T.K</creatorcontrib><creatorcontrib>Wu, Shinn-Chih</creatorcontrib><creatorcontrib>Hung, Che-Ming</creatorcontrib><creatorcontrib>Kuo, Meng-Fu</creatorcontrib><creatorcontrib>Chen, Chuan-Mu</creatorcontrib><title>Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.</description><subject>Allergy and Immunology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antimicrobial agents</subject><subject>Antiviral activity</subject><subject>Antiviral Agents - immunology</subject><subject>Antiviral Agents - metabolism</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Child, Preschool</subject><subject>Cytomegalovirus</subject><subject>Deoxyribonucleic acid</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>Enterovirus</subject><subject>Enterovirus - isolation & purification</subject><subject>Enterovirus - pathogenicity</subject><subject>Enterovirus 71</subject><subject>Enterovirus Infections - mortality</subject><subject>Enterovirus Infections - prevention & control</subject><subject>Enterovirus Infections - virology</subject><subject>Female</subject><subject>Females</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Infections</subject><subject>Lactalbumin - genetics</subject><subject>Lactalbumin - immunology</subject><subject>Lactalbumin - metabolism</subject><subject>Lactation</subject><subject>Lactoferrin - genetics</subject><subject>Lactoferrin - immunology</subject><subject>Lactoferrin - metabolism</subject><subject>Mammals</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Microbiology</subject><subject>Milk</subject><subject>Milk - chemistry</subject><subject>Milk - metabolism</subject><subject>Miscellaneous</subject><subject>Mortality</subject><subject>Neonatal viral infection</subject><subject>Porcine lactoferrin</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - immunology</subject><subject>Recombinant Proteins - metabolism</subject><subject>Rodents</subject><subject>Survival</subject><subject>Swine</subject><subject>Transgenic animals</subject><subject>Transgenic mice</subject><subject>Virology</subject><subject>Yeast</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkl2LEzEUhoMobq3-BCUgeteak0wmMzeKLOsHLAh-gHchzZzZppvJdJO0bv-FP9kMLS7szd4k5PCclzfnPYS8BLYEBvW7zXJvrHUBl5wxtQS-ZCAekRk0Siy4hOYxmTFeV4sK2O8z8iylDWNMCmifkjNoOFM1iBn5-x3tOKxcMCHT7RgnReqNzWOPMbpA8XYbMSXsaHnkNdLB-Ws69jRHE9IVBmdLySLdxjGjzYkGHIPJxh_LfRwHaqjHvC4lWw6P4QrpH5fXFEPGOO5d3CWaD1ukCp6TJ73xCV-c7jn59eni5_mXxeW3z1_PP14urGQqL5RAxirgfb-yTcuxN7wByWVlWqVUZyVXVS2EUqsWDCoDXSX7iq9wGk0DvZiTt0fd4vtmhynrwSWL3pvif5e0Yly2QsGDILR1I3jNCvj6HrgZdzGUT2iQsmlYo4qjOZFHysYxpYi93kY3mHjQwPSUrN7oU7J6SlYD1yXZ0vfqpL5bDdjddZ2iLMCbE2CSNb4v8ViX_nNFqxKSTdyHI4dlunuHUSfrMFjsXCz56W50D1p5f0_Belf2wPhrPGC6-7VOpUH_mNZw2kKmGFSqDOEfljPZ5A</recordid><startdate>20080213</startdate><enddate>20080213</enddate><creator>Chen, Hsiao-Ling</creator><creator>Wang, Li-Chung</creator><creator>Chang, Chi-Hsuan</creator><creator>Yen, Chih-Ching</creator><creator>Cheng, Winston T.K</creator><creator>Wu, Shinn-Chih</creator><creator>Hung, Che-Ming</creator><creator>Kuo, Meng-Fu</creator><creator>Chen, Chuan-Mu</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20080213</creationdate><title>Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71</title><author>Chen, Hsiao-Ling ; Wang, Li-Chung ; Chang, Chi-Hsuan ; Yen, Chih-Ching ; Cheng, Winston T.K ; Wu, Shinn-Chih ; Hung, Che-Ming ; Kuo, Meng-Fu ; Chen, Chuan-Mu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-73e00412ffbc892efa2815254a9777dc527463377b91ae7a1d45f42be251881f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Allergy and Immunology</topic><topic>Animal models</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antimicrobial agents</topic><topic>Antiviral activity</topic><topic>Antiviral Agents - immunology</topic><topic>Antiviral Agents - metabolism</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Child, Preschool</topic><topic>Cytomegalovirus</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>Enterovirus</topic><topic>Enterovirus - isolation & purification</topic><topic>Enterovirus - pathogenicity</topic><topic>Enterovirus 71</topic><topic>Enterovirus Infections - mortality</topic><topic>Enterovirus Infections - prevention & control</topic><topic>Enterovirus Infections - virology</topic><topic>Female</topic><topic>Females</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Infections</topic><topic>Lactalbumin - genetics</topic><topic>Lactalbumin - immunology</topic><topic>Lactalbumin - metabolism</topic><topic>Lactation</topic><topic>Lactoferrin - genetics</topic><topic>Lactoferrin - immunology</topic><topic>Lactoferrin - metabolism</topic><topic>Mammals</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Transgenic</topic><topic>Microbiology</topic><topic>Milk</topic><topic>Milk - chemistry</topic><topic>Milk - metabolism</topic><topic>Miscellaneous</topic><topic>Mortality</topic><topic>Neonatal viral infection</topic><topic>Porcine lactoferrin</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - immunology</topic><topic>Recombinant Proteins - metabolism</topic><topic>Rodents</topic><topic>Survival</topic><topic>Swine</topic><topic>Transgenic animals</topic><topic>Transgenic mice</topic><topic>Virology</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hsiao-Ling</creatorcontrib><creatorcontrib>Wang, Li-Chung</creatorcontrib><creatorcontrib>Chang, Chi-Hsuan</creatorcontrib><creatorcontrib>Yen, Chih-Ching</creatorcontrib><creatorcontrib>Cheng, Winston T.K</creatorcontrib><creatorcontrib>Wu, Shinn-Chih</creatorcontrib><creatorcontrib>Hung, Che-Ming</creatorcontrib><creatorcontrib>Kuo, Meng-Fu</creatorcontrib><creatorcontrib>Chen, Chuan-Mu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & 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Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hsiao-Ling</au><au>Wang, Li-Chung</au><au>Chang, Chi-Hsuan</au><au>Yen, Chih-Ching</au><au>Cheng, Winston T.K</au><au>Wu, Shinn-Chih</au><au>Hung, Che-Ming</au><au>Kuo, Meng-Fu</au><au>Chen, Chuan-Mu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2008-02-13</date><risdate>2008</risdate><volume>26</volume><issue>7</issue><spage>891</spage><epage>898</epage><pages>891-898</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>18207613</pmid><doi>10.1016/j.vaccine.2007.12.013</doi><tpages>8</tpages></addata></record> |
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subjects | Allergy and Immunology Animal models Animals Animals, Newborn Antimicrobial agents Antiviral activity Antiviral Agents - immunology Antiviral Agents - metabolism Biological and medical sciences Body Weight Child, Preschool Cytomegalovirus Deoxyribonucleic acid Disease Models, Animal DNA Enterovirus Enterovirus - isolation & purification Enterovirus - pathogenicity Enterovirus 71 Enterovirus Infections - mortality Enterovirus Infections - prevention & control Enterovirus Infections - virology Female Females Fundamental and applied biological sciences. Psychology HIV Human immunodeficiency virus Humans Infant, Newborn Infections Lactalbumin - genetics Lactalbumin - immunology Lactalbumin - metabolism Lactation Lactoferrin - genetics Lactoferrin - immunology Lactoferrin - metabolism Mammals Mice Mice, Inbred BALB C Mice, Transgenic Microbiology Milk Milk - chemistry Milk - metabolism Miscellaneous Mortality Neonatal viral infection Porcine lactoferrin Recombinant Proteins - genetics Recombinant Proteins - immunology Recombinant Proteins - metabolism Rodents Survival Swine Transgenic animals Transgenic mice Virology Yeast |
title | Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71 |
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