在细胞培养中,与致病性较低的病毒相比,高致病性猴/人免疫缺陷病毒能有效地产生感染性病毒粒子。

Q1 Mathematics
Shoya Iwanami, Yusuke Kakizoe, Satoru Morita, Tomoyuki Miura, Shinji Nakaoka, Shingo Iwami
{"title":"在细胞培养中,与致病性较低的病毒相比,高致病性猴/人免疫缺陷病毒能有效地产生感染性病毒粒子。","authors":"Shoya Iwanami,&nbsp;Yusuke Kakizoe,&nbsp;Satoru Morita,&nbsp;Tomoyuki Miura,&nbsp;Shinji Nakaoka,&nbsp;Shingo Iwami","doi":"10.1186/s12976-017-0055-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains-the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64-and measured the time-course of experimental data in cell culture.</p><p><strong>Methods: </strong>We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains.</p><p><strong>Results and conclusions: </strong>We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID<sub>50</sub>, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID<sub>50</sub>/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.</p>","PeriodicalId":51195,"journal":{"name":"Theoretical Biology and Medical Modelling","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12976-017-0055-8","citationCount":"14","resultStr":"{\"title\":\"A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.\",\"authors\":\"Shoya Iwanami,&nbsp;Yusuke Kakizoe,&nbsp;Satoru Morita,&nbsp;Tomoyuki Miura,&nbsp;Shinji Nakaoka,&nbsp;Shingo Iwami\",\"doi\":\"10.1186/s12976-017-0055-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains-the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64-and measured the time-course of experimental data in cell culture.</p><p><strong>Methods: </strong>We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains.</p><p><strong>Results and conclusions: </strong>We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID<sub>50</sub>, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID<sub>50</sub>/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.</p>\",\"PeriodicalId\":51195,\"journal\":{\"name\":\"Theoretical Biology and Medical Modelling\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-04-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1186/s12976-017-0055-8\",\"citationCount\":\"14\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theoretical Biology and Medical Modelling\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s12976-017-0055-8\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Mathematics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theoretical Biology and Medical Modelling","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s12976-017-0055-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Mathematics","Score":null,"Total":0}
引用次数: 14

摘要

背景:人类免疫缺陷病毒(HIV)的宿主范围很窄。因此,由于缺乏合适的动物模型系统,分析HIV-1在体内的发病机制受到限制。为了克服这一问题,已经开发出编码HIV-1 Env并对猕猴具有传染性的嵌合猴免疫缺陷病毒和人类免疫缺陷病毒(shiv),并用于研究HIV-1在体内的致病性。到目前为止,我们在猕猴实验中有许多SHIV毒株显示出不同的发病机制。然而,艾滋病毒感染的动态方面还没有得到很好的了解。为了充分了解SHIV的动态特性,我们重点研究了两种具有代表性的菌株——高致病性SHIV- ks661和低致病性SHIV-#64,并在细胞培养中测量了实验数据的时间过程。方法:用SHIV-KS661和-#64分别感染HSC-F,测定nef阴性(靶)和nef阳性(感染)HSC-F细胞的浓度、总病毒载量和感染性病毒载量,连续9 d。在两种不同的感染多重度下重复实验,并将先前开发的包含感染性和非感染性病毒的数学模型同时拟合到每个菌株的完整数据集,以表征这两种菌株的感染动力学。结果与结论:对SHIV-KS661和-#64的病毒爆发大小和基本繁殖数等病毒学指标进行了定量分析。比较总病毒和感染性病毒的爆发大小(病毒RNA拷贝数和TCID50),我们发现SHIV-KS661和-#64的感染性病毒爆发大小差异有统计学意义,而总病毒爆发大小差异无统计学意义。此外,我们的分析表明,在产生的SHIV- ks661病毒中,感染性病毒的比例(定义为感染性病毒载量(TCID50/ml)除以总病毒载量(RNA拷贝数/ml))比SHIV-#64在整个感染期间(即9天)高出10倍以上。综上所述,我们得出结论,在细胞培养中,高致病性的SHIV比低致病性的SHIV更有效地产生感染性病毒粒子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.

A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.

A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.

A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.

Background: The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains-the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64-and measured the time-course of experimental data in cell culture.

Methods: We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains.

Results and conclusions: We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID50, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Theoretical Biology and Medical Modelling
Theoretical Biology and Medical Modelling MATHEMATICAL & COMPUTATIONAL BIOLOGY-
自引率
0.00%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Theoretical Biology and Medical Modelling is an open access peer-reviewed journal adopting a broad definition of "biology" and focusing on theoretical ideas and models associated with developments in biology and medicine. Mathematicians, biologists and clinicians of various specialisms, philosophers and historians of science are all contributing to the emergence of novel concepts in an age of systems biology, bioinformatics and computer modelling. This is the field in which Theoretical Biology and Medical Modelling operates. We welcome submissions that are technically sound and offering either improved understanding in biology and medicine or progress in theory or method.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信