Filamentous versus Spherical Morphology: A Case Study of the Recombinant A/WSN/33 (H1N1) Virus

Abstract

Influenza A virus is a serious human pathogen that assembles enveloped virions on the plasma membrane of the host cell. The pleiomorphic morphology of influenza A virus, represented by spherical, elongated, or filamentous particles, is important for the spread of the virus in nature. Using fixative protocols for sample preparation and negative staining electron microscopy, we found that the recombinant A/WSN/33 (H1N1) (rWSN) virus, a strain considered to be strictly spherical, may produce filamentous particles when amplified in the allantoic cavity of chicken embryos. In contrast, the laboratory WSN strain and the rWSN virus amplified in Madin–Darby canine kidney cells exhibited a spherical morphology. Next-generation sequencing (NGS) suggested a rare Ser126Cys substitution in the M1 protein of rWSN, which was confirmed by the mass spectrometric analysis. No structurally relevant substitutions were found by NGS in other proteins of rWSN. Bioinformatics algorithms predicted a neutral structural effect of the Ser126Cys mutation. The mrWSN_M1_126S virus generated after the introduction of the reverse Cys126Ser substitution exhibited a similar host-dependent partially filamentous phenotype. We hypothesize that a shortage of some as-yet-undefined cellular components involved in virion budding and membrane scission may result in the appearance of filamentous particles in the case of usually “nonfilamentous” virus strains.

Characterization of Inactivated Influenza Vaccines Used in the Russian National Immunization Program

“…We used negative-stain transmission electron microscopy (TEM) and dynamic light scattering (DLS) to evaluate the microstructure of IIVs. In interpreting the TEM images obtained, we used the results of previous electron microscopy studies of the influenza virus [37,38], whole inactivated virus vaccines [39], and purified recombinant HA [40,41], as well as TEM images of influenza virions we derived from the virus-containing allantoic fluid ( Figure S21).…”

Non-Negligible Role of Trace Elements in Influenza Virus Infection

“…The influenza virus is classified into four types, including type A, B, C and D. Influenza A virus is the most common type and historic pandemics were all caused by it [ 2 ]. Typically, influenza A is spherical, but filamentous in some cases [ 3 ]. As a member of the Orthomyxoviridae family, influenza A virus is enveloped by a lipid bilayer ( Figure 1 ) [ 4 ].…”