Department of Chemical and Biological Engineering, Wisconsin Institute for Discovery, University of Wisconsin-Madison, 330 N. Orchard Street, Madison, WI 53715, USA.
Viruses. 2022 Feb 14;14(2):383. doi: 10.3390/v14020383.
Virus-like particles resemble infectious virus particles in size, shape, and molecular composition; however, they fail to productively infect host cells. Historically, the presence of virus-like particles has been inferred from total particle counts by microscopy, and infectious particle counts or plaque-forming-units (PFUs) by plaque assay; the resulting ratio of particles-to-PFUs is often greater than one, easily 10 or 100, indicating that most particles are non-infectious. Despite their inability to hijack cells for their reproduction, virus-like particles and the defective genomes they carry can exhibit a broad range of behaviors: interference with normal virus growth during co-infections, cell killing, and activation or inhibition of innate immune signaling. In addition, some virus-like particles become productive as their multiplicities of infection increase, a sign of cooperation between particles. Here, we review established and emerging methods to count virus-like particles and characterize their biological functions. We take a critical look at evidence for defective interfering virus genomes in natural and clinical isolates, and we review their potential as antiviral therapeutics. In short, we highlight an urgent need to better understand how virus-like genomes and particles interact with intact functional viruses during co-infection of their hosts, and their impacts on the transmission, severity, and persistence of virus-associated diseases.
病毒样颗粒在大小、形状和分子组成上与感染性病毒颗粒相似；然而，它们不能有效地感染宿主细胞。从历史上看，病毒样颗粒的存在可以通过显微镜观察到的总颗粒计数，以及通过噬斑测定法观察到的感染性颗粒计数或噬菌斑形成单位（PFU）来推断；由此产生的颗粒与 PFU 的比值通常大于 1，很容易是 10 或 100，表明大多数颗粒是无感染性的。尽管它们不能劫持细胞进行繁殖，但病毒样颗粒及其携带的缺陷基因组可以表现出广泛的行为：在共感染期间干扰正常病毒的生长、细胞杀伤以及先天免疫信号的激活或抑制。此外，一些病毒样颗粒随着其感染复数的增加而变得具有生产力，这是颗粒之间合作的标志。在这里，我们回顾了用于计数病毒样颗粒和表征其生物学功能的现有和新兴方法。我们仔细研究了天然和临床分离物中缺陷干扰病毒基因组的证据，并回顾了它们作为抗病毒治疗剂的潜力。简而言之，我们强调迫切需要更好地了解病毒样基因组和颗粒如何在宿主的共感染期间与完整功能病毒相互作用，以及它们对病毒相关疾病的传播、严重程度和持续存在的影响。
