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Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis
Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the high...
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Published in: | Viruses 2018-11, Vol.10 (11), p.658 |
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description | Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model. |
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Elgon (Musoke) in Macaques: A Pooled Survival Analysis</title><source>Publicly Available Content Database</source><source>PubMed Central(OpenAccess)</source><creator>Blair, Paul W ; Keshtkar-Jahromi, Maryam ; Psoter, Kevin J ; Reisler, Ronald B ; Warren, Travis K ; Johnston, Sara C ; Goff, Arthur J ; Downey, Lydia G ; Bavari, Sina ; Cardile, Anthony P</creator><creatorcontrib>Blair, Paul W ; Keshtkar-Jahromi, Maryam ; Psoter, Kevin J ; Reisler, Ronald B ; Warren, Travis K ; Johnston, Sara C ; Goff, Arthur J ; Downey, Lydia G ; Bavari, Sina ; Cardile, Anthony P</creatorcontrib><description>Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.</description><identifier>ISSN: 1999-4915</identifier><identifier>EISSN: 1999-4915</identifier><identifier>DOI: 10.3390/v10110658</identifier><identifier>PMID: 30469360</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angola ; animal ; Animal models ; Animals ; Anorexia ; Appetite loss ; Clinical trials ; Disease ; Disease Models, Animal ; Ebola virus ; Epidemics ; Exanthema ; Experiments ; Fatalities ; FDA approval ; Filoviridae ; hemorrhagic fevers ; Infectious diseases ; Injections, Intramuscular ; Laboratory animals ; Macaca ; Marburg disease ; Marburg virus disease ; Marburg Virus Disease - pathology ; Marburgvirus ; Marburgvirus - pathogenicity ; Medical laboratories ; Medical research ; mononegavirales ; Musoke ; Phenotypes ; Product development ; Retrospective Studies ; Survival Analysis ; United States ; Vaccines ; viral ; Viremia ; Virulence ; Viruses</subject><ispartof>Viruses, 2018-11, Vol.10 (11), p.658</ispartof><rights>2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-3729a5974ec78df3e3e3a54926f94fe4a6d9b41f018d8654aabd2d99814471603</citedby><cites>FETCH-LOGICAL-c469t-3729a5974ec78df3e3e3a54926f94fe4a6d9b41f018d8654aabd2d99814471603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2582921440/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2582921440?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30469360$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blair, Paul W</creatorcontrib><creatorcontrib>Keshtkar-Jahromi, Maryam</creatorcontrib><creatorcontrib>Psoter, Kevin J</creatorcontrib><creatorcontrib>Reisler, Ronald B</creatorcontrib><creatorcontrib>Warren, Travis K</creatorcontrib><creatorcontrib>Johnston, Sara C</creatorcontrib><creatorcontrib>Goff, Arthur J</creatorcontrib><creatorcontrib>Downey, Lydia G</creatorcontrib><creatorcontrib>Bavari, Sina</creatorcontrib><creatorcontrib>Cardile, Anthony P</creatorcontrib><title>Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis</title><title>Viruses</title><addtitle>Viruses</addtitle><description>Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.</description><subject>Angola</subject><subject>animal</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anorexia</subject><subject>Appetite loss</subject><subject>Clinical trials</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Ebola virus</subject><subject>Epidemics</subject><subject>Exanthema</subject><subject>Experiments</subject><subject>Fatalities</subject><subject>FDA approval</subject><subject>Filoviridae</subject><subject>hemorrhagic fevers</subject><subject>Infectious diseases</subject><subject>Injections, Intramuscular</subject><subject>Laboratory animals</subject><subject>Macaca</subject><subject>Marburg disease</subject><subject>Marburg virus disease</subject><subject>Marburg Virus Disease - pathology</subject><subject>Marburgvirus</subject><subject>Marburgvirus - pathogenicity</subject><subject>Medical laboratories</subject><subject>Medical research</subject><subject>mononegavirales</subject><subject>Musoke</subject><subject>Phenotypes</subject><subject>Product development</subject><subject>Retrospective Studies</subject><subject>Survival Analysis</subject><subject>United States</subject><subject>Vaccines</subject><subject>viral</subject><subject>Viremia</subject><subject>Virulence</subject><subject>Viruses</subject><issn>1999-4915</issn><issn>1999-4915</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1v1DAQhiMEoqVw4A8gS1zawxY7dpwMB6TVqkClrkDi42pN_JFm8caLnazUf4_DllWLfLA1fv3MzOspiteMXnIO9N2eUcaorJonxSkDgIUAVj19cD4pXqS0oVRKoPXz4oRTIYFLelrc_uzj5O2gLQmOrDG2U-zIHExkOXTBI1mF7Q6jNWQMZD1ekivfhYGcr6cUftkL0g_5mcbfk03vyZJ8DcFn7bcp7vs9-gxBf5f69LJ45tAn--p-Pyt-fLz6vvq8uPny6Xq1vFnoXNK44HUJWEEtrK4b47jNCysBpXQgnBUoDbSCOcoa08hKILamNAANE6JmkvKz4vrANQE3ahf7LcY7FbBXfwMhdgrj2GtvVekc6rrVTnIujGwBHJaSOQGQnRIysz4cWLup3Vqj7TBG9I-gj2-G_lZ1Ya9kKWtJmww4vwfEMBs0qm2ftPUeBxumpErGa1EDY3Out_9JN2GK2bysqpoSytzg3N3FQaVjSCladyyGUTXPgjrOQta-eVj9Ufnv8_kfhp-tBQ</recordid><startdate>20181121</startdate><enddate>20181121</enddate><creator>Blair, Paul W</creator><creator>Keshtkar-Jahromi, Maryam</creator><creator>Psoter, Kevin J</creator><creator>Reisler, Ronald B</creator><creator>Warren, Travis K</creator><creator>Johnston, Sara C</creator><creator>Goff, Arthur J</creator><creator>Downey, Lydia G</creator><creator>Bavari, Sina</creator><creator>Cardile, Anthony P</creator><general>MDPI AG</general><general>MDPI</general><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>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20181121</creationdate><title>Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis</title><author>Blair, Paul W ; Keshtkar-Jahromi, Maryam ; Psoter, Kevin J ; Reisler, Ronald B ; Warren, Travis K ; Johnston, Sara C ; Goff, Arthur J ; Downey, Lydia G ; Bavari, Sina ; Cardile, Anthony P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-3729a5974ec78df3e3e3a54926f94fe4a6d9b41f018d8654aabd2d99814471603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Angola</topic><topic>animal</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anorexia</topic><topic>Appetite loss</topic><topic>Clinical trials</topic><topic>Disease</topic><topic>Disease Models, Animal</topic><topic>Ebola virus</topic><topic>Epidemics</topic><topic>Exanthema</topic><topic>Experiments</topic><topic>Fatalities</topic><topic>FDA approval</topic><topic>Filoviridae</topic><topic>hemorrhagic fevers</topic><topic>Infectious diseases</topic><topic>Injections, Intramuscular</topic><topic>Laboratory animals</topic><topic>Macaca</topic><topic>Marburg disease</topic><topic>Marburg virus disease</topic><topic>Marburg Virus Disease - pathology</topic><topic>Marburgvirus</topic><topic>Marburgvirus - pathogenicity</topic><topic>Medical laboratories</topic><topic>Medical research</topic><topic>mononegavirales</topic><topic>Musoke</topic><topic>Phenotypes</topic><topic>Product development</topic><topic>Retrospective Studies</topic><topic>Survival Analysis</topic><topic>United States</topic><topic>Vaccines</topic><topic>viral</topic><topic>Viremia</topic><topic>Virulence</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blair, Paul W</creatorcontrib><creatorcontrib>Keshtkar-Jahromi, Maryam</creatorcontrib><creatorcontrib>Psoter, Kevin J</creatorcontrib><creatorcontrib>Reisler, Ronald B</creatorcontrib><creatorcontrib>Warren, Travis K</creatorcontrib><creatorcontrib>Johnston, Sara C</creatorcontrib><creatorcontrib>Goff, Arthur J</creatorcontrib><creatorcontrib>Downey, Lydia G</creatorcontrib><creatorcontrib>Bavari, Sina</creatorcontrib><creatorcontrib>Cardile, Anthony P</creatorcontrib><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>Virology and AIDS Abstracts</collection><collection>ProQuest - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Viruses</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blair, Paul W</au><au>Keshtkar-Jahromi, Maryam</au><au>Psoter, Kevin J</au><au>Reisler, Ronald B</au><au>Warren, Travis K</au><au>Johnston, Sara C</au><au>Goff, Arthur J</au><au>Downey, Lydia G</au><au>Bavari, Sina</au><au>Cardile, Anthony P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis</atitle><jtitle>Viruses</jtitle><addtitle>Viruses</addtitle><date>2018-11-21</date><risdate>2018</risdate><volume>10</volume><issue>11</issue><spage>658</spage><pages>658-</pages><issn>1999-4915</issn><eissn>1999-4915</eissn><abstract>Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30469360</pmid><doi>10.3390/v10110658</doi><oa>free_for_read</oa></addata></record> |
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subjects | Angola animal Animal models Animals Anorexia Appetite loss Clinical trials Disease Disease Models, Animal Ebola virus Epidemics Exanthema Experiments Fatalities FDA approval Filoviridae hemorrhagic fevers Infectious diseases Injections, Intramuscular Laboratory animals Macaca Marburg disease Marburg virus disease Marburg Virus Disease - pathology Marburgvirus Marburgvirus - pathogenicity Medical laboratories Medical research mononegavirales Musoke Phenotypes Product development Retrospective Studies Survival Analysis United States Vaccines viral Viremia Virulence Viruses |
title | Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis |
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