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Friday, March 22, 2013

For better viral transmission, have a defective partner

We have extensive correction and repair mechanisms in our cells to keep our DNA error free. Viruses, being minimalists, tend to skip such extraneous functions. For better or worse (and it works both ways for them), viruses tend to accumulate mutations at a high rate. This also means that a fair number of new viruses are altered to the point of being ‘defective’. That is, they lack the necessary equipment to complete their life cycle (for the sake of argument, I’ll consider viruses to be alive). Are these defects ejected from the gene pool? Not so fast, say Ruian Ke of UCLA and his colleagues.

While it is true that defective viruses are useless on their own, if they happen to co-infect a cell with a functional virus, they can use the working genes from the second virus to complement whatever capabilities they lack. But that’s not the interesting bit. It turns out that for Dengue viruses, the presence of defective viruses helps the normal viruses spread more effectively.

Image of a Dengue virus.
Source: Virusworld.

This was a surprise because defective viruses were thought to hinder their normal counterparts by depleting the resources of the infected cell. A cell infected with both defective and normal viruses should make enough defective viruses that can’t infect other cells to cause the infection to wind down. Instead, the defective Dengue viruses significantly increased the transmissibility of the normal virus. In fact, Ke and his colleagues traced the start of some Dengue epidemics to the appearance of specific defective virus strains.

So how does this work? That’s still unknown. However, one intriguing possibility is that the defective viruses do interfere with normal viruses and decrease the number of infectious agents just as suspected. As a consequence, the infected individuals don’t feel as sick and are that much more likely to interact with other people and spread the infection. In this scenario, there are fewer functional viruses made, but the virus wins anyway because it still gets circulated.

If these findings prove true for other viruses, they could have broad-ranging implications for the study of infectious viruses. To be clear, defective viruses can only cause trouble if they co-infect a cell with a complementary intact virus. We don't know how often this happens. In any case, researchers and doctors will no longer be able to dismiss defective viruses as unimportant to epidemiology. 

Ke, R., Aaskov, J., Holmes, E., & Lloyd-Smith, J. (2013). Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses PLoS Pathogens, 9 (2) DOI: 10.1371/journal.ppat.1003193.

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