When a virus jumps from wildlife to humans, it could either cause a few infections and fizzle out—or it could spark an explosive outbreak. For instance, health experts feared that H5N1 bird flu would lead to a massive and deadly pandemic in humans in the early 2000s, but with its current limited ability to jump from human to human, it has yet to kick off such a large-scale plague. Zika, Ebola, and HIV/AIDS, on the other hand, have.
Figuring out beforehand the type of viral scenario that will unfold with a new, emerging germ would be vital to protecting public health, allowing health officials to anticipate and thwart the spread of infections before they get out of hand. But researchers have largely struggled with how to make those predictions.
To try to break down the molecular recipe for a pandemic, researchers analyzed a range of biological features from 203 human-infecting viruses—a mix of those that have and have not caused big outbreaks. The researchers aimed to find predictors of infectious potential among each virus’ characteristics, including its family tree; genome’s make-up (DNA or RNA), length, and segmentation; outer structure of its viral particle; tendency to recombine with relative viruses and create variation in its genetics; time spent in a victim; deadliness; and whether or not it spreads via a vector, such as mosquitoes and ticks. The results appear in the Proceedings of the National Academy of Sciences.
Surprisingly, the researchers found that the segmented genomes and the genetic tendency to recombine were not good predictors of a virus’ pandemic potential. This data falls in line with the dead-end infections of H5N1, which has a segmented genome that easily recombines.
The factors that were good predictors of pandemic potential include the ability to keep a victim alive for a while, perhaps for life, so that the infected can keep spreading the infection. Also, having a non-enveloped outer structure was a good predictor. This may be because lacking a protective coating like an envelope gives inner viral proteins more opportunity to interact with and infect a variety of cells they bump into—including human cells.
But the strongest predictor of pandemic potential was direct transmission from person to person, without vector transmission being involved—highlighting the fact that the mosquito-transmitted Zika virus is an oddity.
Of the 69 vector-borne, human-infecting viruses included in the study, only six have the potential to spread from person to person. This may be because many of those 69 viruses also infect populations of wild animals—known as “reservoirs.” While such reservoir populations may give viruses constant opportunities to build up numbers and spill out to infect people, switching to a new host, such as a human, is a biological hurdle. In instances when a virus does make the leap to a human, it doesn’t often adapt to infect more humans.
Zika, first identified in monkeys, is the only vector-transmitted virus that appears to be able to completely break out of its reservoir-vector cycle and spread independently between humans via sexual transmission, the authors noted.
Despite the exception, the authors are hopeful that the analysis can help with future predictions of emerging viruses. “By identifying the major biological features of successfully emerging viruses, our analysis can be used to generate broad-scale predictions of the likelihood that a virus of a specific family will achieve human-to-human transmission and thus epidemic spread,” the authors conclude.