Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus.
Establishing an In Vitro System to Assess How Specific Antibodies Drive the Evolution of Foot-and-Mouth Disease Virus.
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DOI：
10.3390/v14081820
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发表时间：
2022-08-19
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影响因子：
--
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病毒可以进化以响应接种疫苗和/或感染后产生的特异性抗体所赋予的免疫压力。在这项研究中，在体外系统的开发，以调查血清中和抗体后的口蹄疫病毒（FMDV）分离株的演变的影响。与未处理的对照培养物相比，特异性抗血清的亚中和稀释液的存在将病毒诱导的细胞病变效应（CPE）的发生延迟长达44小时。用这些血清的亚中和稀释液继续病毒传代导致完成CPE的时间减少，表明这些培养物中的FMDV适应于逃避免疫压力。这些表型变化与病毒RNA编码氨基酸VP 266、VP 280和VP 1155位置（对应于已知表位位点）的三个独立的共识水平非同义突变相关。高通量测序还鉴定了编码前导（Lpro）、VP 4、VP 2和VP 3蛋白的区域内的进一步核苷酸取代。虽然后来的突变与适应免疫压力的关联必须进一步验证，但这些结果突出了FMDV群体可以逃避中和抗体的多种途径，并支持应用简单的体外方法来评估体液免疫系统对FMDV和潜在的其他病毒进化的影响。
Viruses can evolve to respond to immune pressures conferred by specific antibodies generated after vaccination and/or infection. In this study, an in vitro system was developed to investigate the impact of serum-neutralising antibodies upon the evolution of a foot-and-mouth disease virus (FMDV) isolate. The presence of sub-neutralising dilutions of specific antisera delayed the onset of virus-induced cytopathic effect (CPE) by up to 44 h compared to the untreated control cultures. Continued virus passage with sub-neutralising dilutions of these sera resulted in a decrease in time to complete CPE, suggesting that FMDV in these cultures adapted to escape immune pressure. These phenotypic changes were associated with three separate consensus-level non-synonymous mutations that accrued in the viral RNA-encoding amino acids at positions VP266, VP280 and VP1155, corresponding to known epitope sites. High-throughput sequencing also identified further nucleotide substitutions within the regions encoding the leader (Lpro), VP4, VP2 and VP3 proteins. While association of the later mutations with the adaptation to immune pressure must be further verified, these results highlight the multiple routes by which FMDV populations can escape neutralising antibodies and support the application of a simple in vitro approach to assess the impact of the humoral immune system on the evolution of FMDV and potentially other viruses.
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影响因子：
9.4
作者：
LaRocco, Michael;Krug, Peter W.;Rodriguez, Luis L.
通讯作者：
Rodriguez, Luis L.
影响因子：
3.8
作者：
BOLWELL, C;CLARKE, BE;ROWLANDS, DJ
通讯作者：
ROWLANDS, DJ
DOI：
10.2460/javma.2002.220.1636
发表时间：
2002-06-01
期刊：
JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
影响因子：
--
作者：
Callahan, JD;Brown, F;Nelson, WM
通讯作者：
Nelson, WM
DOI：
10.1073/pnas.96.24.13910
发表时间：
1999-11-23
影响因子：
11.1
作者：
Drake, JW;Holland, JJ
通讯作者：
Holland, JJ
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.