The latest paper by the Brooke lab investigates the mechanism through which an Influenza A-infected host cell can be rendered resistant to subsequent viral infections. The findings were published in a paper titled “Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity” in mBio.
Influenza A viruses are notorious for their high infection rates during seasonal epidemics. Even though vaccines are developed each year, the viruses can evolve rapidly, sometimes rendering the vaccines ineffective. Therefore, there is a constant race between the virus and vaccine developers.
The evolution of these viruses is heavily influenced by the fact that their genetic information has an unusual arrangement. It is encoded on eight discrete pieces of RNA and expression of all genes are essential for productive infection. However, the majority of influenza A virus particles do not contain a full set of genetic material and are therefore defective in their ability to cause a productive infection.
It is common for multiple viruses, with incomplete genetic information, to infect the same cell. However, allowing them to collectively reconstitute the complete set of viral genetic material is needed for productive infection. This phenomenon is known as co-infection. In some cases, co-infection can result in reassortment, where viral particles exchange complete RNA segments and generate new viruses.
“Co-infection by incomplete viruses enables the formation of the complete viral genome, resulting in a successful infection,” explained Jiayi Sun, a graduate student in the Brooke lab. “On the other hand, complete viruses resist co-infection.” The paper investigates what factors impair co-infection.
It was previously suggested by other labs that co-infection is blocked by the production of neuraminidase, an enzyme that cleaves the viral receptors on the host cell so that subsequent viruses cannot enter the host. However, this paper offers a different mechanism. “Our model is during the primary infection the expression of the viral polymerase inhibits further infections,” explained Sun.
“It remains unclear how the polymerase causes inhibition. It could be that an anti-viral response is triggered in the host in response to the polymerase,” said Dr. Christopher Brooke, Assistant Professor in the Department of Microbiology. “It is clear, however, that viral particles that have a higher number of gene segments show higher polymerase activity and increased resistance to co-infection.”
Co-infection can have dangerous consequences. When reassortment involves the mixing of different viral strains, there is always a tiny chance that a new strain will emerge that could potentially give rise to a pandemic. “Co-infection drives viral evolution. By understanding co-infection, we can gain insight into how these viruses evolve,” said Brooke. “Until we understand this fundamental process, we will struggle to develop a more effective vaccine.”
