How Narrow Is the Gas Phase Mobility Distribution of Enveloped Viruses? The Case of the Φ6 Bacteriophage

Abstract

We use the Φ6 bacteriophage previously exploited as a BSL-1 surrogate of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS) coronavirus to obtain the first high-resolution gas phase mobility spectra of an enveloped virus. The relative full width at half-maximum found for the viral mobility distribution (FWHM Z < 3.7%) is substantially narrower than that reported by prior mobility or microscopy studies with other enveloped viruses. It is nevertheless not as narrow as that recently found for several non-enveloped viruses (FWHM Z ≈ 2%), presumably due to particle to particle variability of enveloped viruses. This 3.7% is an upper bound to the actual width. Nevertheless, the well-defined mobility peaks obtained indicate that gas phase mobility analysis is a more discriminating methodology than that previously demonstrated for physically based non-genetic viral diagnostic of enveloped viruses. These results are obtained by analysis of the original cell culture medium containing the virus, purified only by passage through a 0.22 μm filter and by dialysis into a 10 mM aqueous ammonium acetate buffer. We confirmed that this buffer exchange preserves infectivity. Therefore, the 63.7 nm mobility diameter found, although smaller than the 75 nm previously inferred by microscopy, corresponds to the full particle including the envelope.

Spontaneous Interconversion between Different Narrowly Defined Shapes of Rotavirus Double-Layered Particles Studied in Real Time by High-Resolution Mobility Analysis

“…Whatever its cause, the mismatch between the sizes determined by electron microscopy and the mobility is not unique to our study. Comparable differences have been found by Fernandez de la Mora et al, who report a mobility diameter of 63.7 nm for the enveloped bacteriophage Φ6, for which microscopy measurements had previously given 75 nm. A study relying on mobility as well as several microscopy techniques has found similar differences, with a mobility diameter always smaller than the microscopy value.…”

“…This presumed double compaction would, on the one hand, be driven by capillary stresses arising in the gas phase and would, on the other hand, be enabled by the partially empty SLP interior (not all inner space is occupied by the viral genome). Such collapses are common in thin shells under stress and have been invoked in biophysical modeling of viral capsids. ,, In a forthcoming study, we will argue that empty capsids often buckle in the gas phase into a broad range of shapes, resulting in a broad mobility distribution (i.e., the satellite peak in Figure a). The notion that our gas-phase structures have undergone a partial collapse yet have narrow mobility distributions therefore requires some explanation.…”

“…Such collapses are common in thin shells under stress and have been invoked in biophysical modeling of viral capsids. 23,24,29 In a forthcoming study, we will argue that empty capsids often buckle in the gas phase into a broad range of shapes, resulting in a broad mobility distribution (i.e., the satellite peak in Figure 2a). The notion that our gas-phase structures have undergone a partial collapse yet have narrow mobility distributions therefore requires some explanation.…”

Development and Application of a Polydimethylsiloxane-Based Passive Air Sampler to Assess Personal Exposure to SARS-CoV-2

“…The bacteriophage Phi6 (Φ6) was used as a BSL-1 surrogate organism to estimate the rate of uptake of virus-laden aerosols by PDMS. ,, Φ6 has previously been explored as a surrogate for various enveloped viruses in environmental exposure and persistence studies ,− and was recently utilized as a surrogate for SARS-CoV-2 because its physiological characteristics are similar to those of the virus, including a diameter ranging from 75 to 100 nm (vs a diameter of 90–110 nm for SARS-CoV-2), a spherical shape with protruding spike proteins, a lipid envelope, and an RNA genome. ,,, …”

“…The bacteriophage Phi6 (Φ6) was used as a BSL-1 surrogate organism to estimate the rate of uptake of virus-laden aerosols by PDMS. 10,26,27 Φ6 has previously been explored as a surrogate for various enveloped viruses in environmental exposure and persistence studies 10,28−30 and was recently utilized as a surrogate for SARS-CoV-2 because its physiological characteristics are similar to those of the virus, including a diameter ranging from 75 to 100 nm (vs a diameter of 90−110 nm for SARS-CoV-2), 31 a spherical shape with protruding spike proteins, a lipid envelope, and an RNA genome. 10,26,32,33 Rotating Drum Configuration, Aerosol Generation, and Aerosol Sampling.…”