Time lapse movies of fluorescent viruses entering cells. The cells express fluorescent receptors (shown in green) and this shows us how viruses (shown in red) enter and infect cells in the body.
Image. An RSV viral particle (red) about to infect a cell by binding to its nucleolin coreceptor (green). For further information please refer to our paper Griffiths and Bilawchuk et al. Nature volume 583, pages 615–619 (2020).
Description of what you are seeing in the video: The RSV particle is labelled in red by a dye that fluoresces more as fusion and virus entry take place. You see it here, first, bound to the RSV coreceptor NCL that is tagged with a green fluorescent protein. As the virus particle fuses with the host cell membrane the dye is released and fluoresces more; it gets brighter. As it disperses through the cell membrane it then gets faint again until it can no longer be seen. This is the first step of virus entry, fusion of the virus and cell membranes to release the contents of the virus particle into the host cell.
Preprint
Respiratory Syncytial Virus Evolution by Adaptation
Farah Elawar, Ahmed Oraby and Aleksandra Stojic et al. and David J. Marchant
Abstract. Respiratory syncytial virus (RSV) infection is the most common cause of infant hospitalizations worldwide, and in the absence of an RSV vaccine, antibody prophylaxis is the only means of protection. The two types of RSV, RSVA and RSVB, share a high level of amino acid identity but they have different serum neutralization profiles. Here, we describe a single amino acid at position 305 in the RSV fusion glycoprotein (RSV-F) that switches the profile from RSVA (Leucine-L) to RSVB (Isoleucine-I). We found that the L305I mutation caused protein-wide shape-shift, altering both antibody and patient serum neutralization susceptibility. We show that viral replication in the presence of selective pressure forces mutation at position 305 and was the only amino acid mutation to occur in RSVA at evolutionary bottlenecks. We also identified a new mutation in RSVB that was associated with pressure from antibody neutralization. We engineered the L305I mutation in an RSV reverse genetic model system that led to a switch in susceptibility between RSVA and B patient sera. We postulate that this event was a significant determinant in the divergence of RSVA and RSVB from the parent virus, and a new mutation in RSVB suggests these viruses are still diverging. Our work suggests that the most effective sterilizing antiviral immunity leads to more rapid virus mutation and immune evasion that applies to RSV treatment, vaccines, and surveillance.