Flegel Timothy W
Center of Excellence for Shrimp Molecular Biology and Biotechnology (Centex Shrimp), Mahidol University, Rama 6 Road, Bangkok 10400, Thailand.
Biol Direct. 2009 Sep 2;4:32. doi: 10.1186/1745-6150-4-32.
It is known that crustaceans and insects can persistently carry one or more viral pathogens at low levels, without signs of disease. They may transmit them to their offspring or to naïve individuals, often with lethal consequences. The underlying molecular mechanisms have not been elucidated, but the process has been called viral accommodation. Since tolerance to one virus does not confer tolerance to another, tolerance is pathogen-specific, so the requirement for a specific pathogen response mechanism (memory) was included in the original viral accommodation concept. Later, it was hypothesized that specific responses were based on the presence of viruses in persistent infections. However, recent developments suggest that specific responses may be based on viral sequences inserted into the host genome.
Non-retroviral fragments of both RNA and DNA viruses have been found in insect and crustacean genomes. In addition, reverse-transcriptase (RT) and integrase (IN) sequences are also common in their genomes. It is hypothesized that shrimp and other arthropods use these RT to recognize "foreign" mRNA of both RNA and DNA viruses and use the integrases (IN) to randomly insert short cDNA sequences into their genomes. By chance, some of these sequences result in production of immunospecific RNA (imRNA) capable of stimulating RNAi that suppresses viral propagation. Individuals with protective inserts would pass these on to the next generation, together with similar protective inserts for other viruses that could be amalgamated rapidly in individual offspring by random assortment of chromosomes. The most successful individuals would be environmentally selected from billions of offspring.
This hypothesis for immunity based on an imRNA generation mechanism fits with the general principle of invertebrate immunity based on a non-host, "pattern recognition" process. If proven correct, understanding the process would allow directed preparation of vaccines for selection of crustacean and insect lines applicable in commercial production species (e.g., shrimp and bees) or in control of insect-borne diseases. Arising from a natural host mechanism, the resulting animals would not be artificially, genetically modified (GMO).
已知甲壳类动物和昆虫能够以低水平持续携带一种或多种病毒病原体,且无疾病迹象。它们可能将这些病原体传播给后代或未感染的个体,通常会产生致命后果。其潜在的分子机制尚未阐明,但这一过程被称为病毒容纳。由于对一种病毒的耐受性并不赋予对另一种病毒的耐受性,耐受性是病原体特异性的,因此在最初的病毒容纳概念中纳入了对特定病原体反应机制(记忆)的要求。后来,有人推测特定反应是基于持续性感染中病毒的存在。然而,最近的进展表明,特定反应可能基于插入宿主基因组的病毒序列。
在昆虫和甲壳类动物基因组中发现了RNA和DNA病毒的非逆转录病毒片段。此外,逆转录酶(RT)和整合酶(IN)序列在它们的基因组中也很常见。据推测,虾和其他节肢动物利用这些RT识别RNA和DNA病毒的“外来”mRNA,并利用整合酶(IN)将短cDNA序列随机插入它们的基因组。偶然地,其中一些序列会导致产生能够刺激RNA干扰从而抑制病毒传播的免疫特异性RNA(imRNA)。具有保护性插入序列的个体将把这些序列传递给下一代,同时还有针对其他病毒的类似保护性插入序列,这些序列可以通过染色体的随机组合在个体后代中迅速合并。最成功的个体将从数十亿后代中通过环境选择产生。
这种基于imRNA产生机制的免疫假说符合基于非宿主“模式识别”过程的无脊椎动物免疫的一般原则。如果被证明是正确的,理解这一过程将有助于有针对性地制备疫苗,以选择适用于商业生产物种(如虾和蜜蜂)或控制虫媒疾病的甲壳类动物和昆虫品系。由于这是一种天然宿主机制,由此产生的动物不会是人工基因改造生物(GMO)。