For over 50 years the RNA genome of picornaviruses (illustrated below for poliovirus) was thought to be translated into a single, long polyprotein. All this time a very small upstream open reading frame (uORF) has gone undetected – until now.
Virus infections initiate when virions bindÂ to receptors on the cell surface.Â It is well known that cells can be made susceptible to infection by providing DNAÂ encoding the virus receptor. For example, mice cannot be infectedÂ with poliovirus, but become susceptible ifÂ they are given the human poliovirus receptor gene. Now we have learned that providing the receptor protein isÂ sufficient to make cells susceptible to infection (link to paper).
Bacteriophages determine the composition of microbial populations by killing some bacteria and sparing others.Â Bacteriophages are typically host specific, a property that is largely determined at the level of attachment to host cell receptors.Â How resistant and sensitive bacteria in mixed communities respond to phage infection has not been well studied.
Several phagesÂ (including SPP1, pictured) of the soil bacterium Bacillus subtilis first attach toÂ poly-glycosylated teichoic acids (gTA), and then to the membrane protein YueB, leading to injection of DNA into the cell. Cells that lack the gene encoding either of these proteins areÂ resistant to infection.
When a mixed culture of resistant and susceptible B. subtilis cells wereÂ infected with phage SPP1, both types of cells became infected and killed. Infection of resistant cells depended on the presence of susceptible cells, because no infection occurred in pure cultures ofÂ resistant cells.
Both infected and uninfected bacteria release small membrane vesicles that contain proteins, nucleic acids, and other molecules. Phage SPP1 can attach to Â membrane vesicles released by susceptible strains of B. subtilis, showing that they contain viral receptor proteins. Furthermore, phage SPP1 can infect resistant cells that have been incubated with membrane vesicles from a susceptible strain – in the absence of intactÂ susceptible cells.
These results show that membrane vesicles released by susceptible bacteria contain viral receptors that can be inserted into the membrane ofÂ a resistant cell, allowing infection. Because phage infection can lead to transfer of host DNA from one cell to another, the results have implications for the movement of genes for antibiotic resistance or virulence. It’s possible that such genes may move into bacteria that have only ‘temporarily’ received virus receptors via membrane vesicle transfer.
These findings should also be considered when designingÂ phage therapy forÂ infectious diseases. The idea is to utilize phages that are host specific and can only destroy the disease-producing bacteria. It’s possible that the host range of suchÂ phages could be expanded by receptor protein transfer. As a consequence,Â unwanted genes might make their way intoÂ ‘resistant’ bacteria.
I wonder if membrane vesicle mediated transfer of receptors also occurs in eukaryotic cells. TheyÂ shed membrane vesicles called exosomes, which contain protein and RNA thatÂ are delivered to other cells. If exosomes bear receptors for viruses, they might be able to deliver the receptors to cells that would not normally be infected. The types of cells infected by a virus would thereby be expanded, potentially affecting the outcome of viral disease.