Robinson L, Knight-Jones T J D, Charleston B, Rodriguez L L, Gay C G, Sumption K J, Vosloo W
Insight Editing London, London, UK.
International Livestock Research Institute (ILRI), Lusaka, Zambia.
Transbound Emerg Dis. 2016 Jun;63 Suppl 1:63-71. doi: 10.1111/tbed.12520.
We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain distribution. With ongoing advances, these areas could translate into significantly improved disease control.
我们通过进行文献综述（2011 - 2015年）并收集来自全球33个机构的研究进展（2014年），评估了口蹄疫病毒（FMDV）发病机制和分子生物学领域的研究知识空白。研究结果用于确定未来研究的优先领域。FMDV发病机制方面已有重要进展；FMDV存在于许多康复动物的淋巴结中，这些动物在其他方面似乎并未持续感染，即使在以前与携带状态无关的物种中也是如此。病毒留存是否有助于维持宿主免疫力和/或病毒存活尚不清楚。野生动物中FMDV发病机制的研究为地方病和流行病环境中的疾病流行病学提供了见解。FMDV感染和病毒进入的许多方面仍不清楚；然而，在细胞水平上，我们知道整合素（允许病毒进入）的表达水平和可用性、受感染细胞的清除率以及抗病毒I型干扰素（IFN）反应的强度是组织嗜性的关键决定因素。将研究结果扩展以更好地理解传播需要一种标准化方法，并在实验研究中采用自然感染途径。自噬体对于FMDV在细胞表面受体结合后进入细胞质的重要性已得到认可，并且不同的细胞内膜被用于病毒复制和免疫逃避。已确定病毒蛋白在阻断I型干扰素产生和下游信号传导方面的新作用，这有助于抗病毒治疗学的研究。我们对感染如何影响细胞蛋白质表达了解得更多，对衣壳稳定性分子决定因素的研究有助于开发稳定的疫苗。我们对病毒和宿主毒力及传染性的分子决定因素，以及系统发育学如何用于估计疫苗匹配度和毒株分布的了解不断增加。随着不断取得进展，这些领域可能会转化为疾病控制的显著改善。
