Enteroviral Transmission Fact Sheet

Q. What did the researchers discover?

A. The NHLBI-funded researchers discovered a novel means by which viruses spread between cells: multiple polioviruses, a type of enterovirus, travel together within a membrane-enclosed sac, arriving together at a cell they then infect.

Q. How do the viral clusters form?

A. After the viruses reproduce themselves within an infected cell, an autophagosome-like organelle engulfs multiple viral particles. Normally, autophagosomes serve as a cellular recycling center, ingesting damaged proteins or excess cellular parts and fusing with a lysosome that contains enzymes that break down the defective cellular parts. However, the researchers found that autophagosomes that had ingested enteroviruses did not fuse with a lysosome but instead were diverted to the host cell’s plasma membrane, the cell’s outer perimeter. There, the double-membraned autophagosome fused with the host cell plasma membrane and released the viral particles, wrapped within the autophagosome’s inner membrane. So enclosed by the membrane, the viral clusters then infected other cells.

Q. What are the advantages of this mode of transmission for the viruses?

A. This novel means of transmission holds several advantages for the enteroviruses. First, it improves infection efficiency. Second, by infecting cells together as a cluster, the viruses ensure that collectively, if not individually, they possess the genetic instructions to successfully reproduce. Although each viral particle has genetic instructions in the form of an RNA genome, these genomes are subject to a high mutation rate, and as a result, some genomes may not produce viable proteins. But because in this mode of transmission multiple viruses infect a cell together, there is a greater chance that at least some of the viruses will produce functioning proteins that other viral particles can then share to accomplish viral replication. Third, by cloaking themselves in a membrane derived from a cellular organelle, the viral particles may be able to travel in disguise between cells, appearing to immune cells not as foreign invaders but as “self”—part of the body.

Q. Was this basic research or translational research?

A. The researchers conducted basic research into the mode of transmission of enteroviruses, hoping to better understand viral transmission between cells. As is the case with most basic research, though, their refined understanding of basic biological processes suggests new approaches to clinical treatments: in particular, the researchers’ discoveries point to approaches to preventing enteroviral infections.

Q. Why is it important to understand transmission of enteroviruses between cells?

A. Enteroviruses are responsible for a number of diseases, including myocarditis (heart inflammation), polio, the common cold, and the respiratory illness caused by Enterovirus D68 (a virus that recently had an outbreak). Understanding enteroviral transmission will help scientists as they seek new ways to treat and prevent these sometimes devastating infections.