Virus-like Particles: Measures and Biological Functions.

Tara Bhat,Amy Cao,John Yin

doi:10.3390/v14020383

Tara Bhat, Amy Cao + Show 1 more

Open Access

https://doi.org/10.3390/v14020383

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Abstract

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.

Highlights

When multiple observations or measures can be made on the same or related phenomena, their combination or comparison may lead to new understanding or insights
The development of foci-forming [3] and plaque-forming assays [4] enabled the quantitative measures of infectious virus particle levels as foci-forming or plaque-forming units (PFUs); when such measures were combined with estimates of total virus-like particles, initially employing electron microscopy [5], the tally of particle-to-PFU ratios that differed from unity showed that most virus-like particles were not infectious
Virologists are aware that different viruses can exhibit very different particle-to-PFU ratios, it is not so widely known that non-infectious virus-like particles can exhibit a diversity of biological activities

Summary

Introduction

When multiple observations or measures can be made on the same or related phenomena, their combination or comparison may lead to new understanding or insights. For example, multiple measures of planetary positions across seasons provided compelling evidence for a universe that was heliocentric rather than geocentric [1]. The diversity of finches observed within and between different islands provided evidence for Darwin’s theory on the origin of species [2]. Particle-to-PFU ratios have ranged from 1-or-2 for bacteriophages and vaccinia virus [6] to 10 for herpes virus [7], 20-to-50 for influenza and 30-to-1000 for poliovirus [8], to 40,000 for varicella zoster virus [9]. Virologists are aware that different viruses can exhibit very different particle-to-PFU ratios, it is not so widely known that non-infectious virus-like particles can exhibit a diversity of biological activities. We focus here on non-infectious virus-like particles that arise as byproducts of virus growth

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