This blog post is provided by Rob Graham (@DrRIGraham) and Ken Wilson (@spodoptera007) and tells the #StoryBehindThePaper for the paper “Trans-generational viral transmission and immune priming are dose-dependent”, which was recently published in Journal of Animal Ecology. The authors found that vertical transmission of virus and priming of the immune system are both dependent on the magnitude of the viral challenge in an insect-pathogen system.

Armyworms are important caterpillar crop pests in Africa and, in the early 1990s, Ken was a young postdoc based in Kenya studying the migration of adult armyworm moths*. As part of this, he would visit lots of high-density armyworm ‘outbreaks’. What struck him most during these visits was that at some outbreaks all of the caterpillars appeared healthy and vigorous, whereas at others there were high levels of viral disease, and it was puzzling what was causing these apparently random epidemics of virus. A mere 30 years later, we think we have the answer, which we report in our latest paper “Trans-generational viral transmission and immune priming are dose-dependent”.

Baculoviruses are a group of viruses closely associated with insects across several Orders, but mainly with members of the Lepidoptera. Since the 1960s, it had been observed that spontaneous disease could sometimes occur in laboratory cultures, even when there was little or no chance of virus contamination. So where did this disease come from? It was believed that insects harboured the ‘covert’ virus themselves and could transmit it ‘vertically’ from parent to offspring, thereby maintaining infection in a population. And some form of ‘trigger’ was then causing the covert infection to become an overt infectious disease.

Since the 1990s onwards (specifically since the advent of PCR, which made it easier to detect viruses) it has become widely accepted that Lepidoptera harbour what we call ‘covert’ infections, and that these can be transmitted from parent to offspring. What is not so clear is the factors impacting trans-generational transmission and what can trigger low-level covert infections to develop into full-blown lethal disease.

African armyworms are found throughout sub-Saharan Africa, but especially in East Africa, and during the dry season there is very little vegetation and caterpillars are scarce – in fact, you would struggle to find one! This not only raises the question of how do the armyworms survive these hostile conditions, but also how does a virus (that traditionally was believed only to be transmitted in a ‘horizontal’ manner – between caterpillars) also survive such low densities of hosts. The working hypothesis was that these viruses must be transmitted vertically when the host is at very low densities, but could somehow revert (or be triggered) to an overt form when conditions become more favourable (i.e. in populations of high host density that will allow some degree of horizontal transmission).

Until fairly recently, it was generally accepted that the invertebrate immune system lacked the ‘immune memory’ that typifies the vertebrate adaptive immune response. In the last couple of decades, however, it has become apparent that invertebrates also have a form of immune memory and that this can be passed from generation to generation, in a process known as trans-generational immune priming (TGIP).

So how would these two trans-generational processes (immune priming and vertical virus transmission) interact, and could this interaction help explain the apparently spontaneous virus epidemics in the field?

This is what we set out to investigate in the laboratory, as reported in Journal of Animal Ecology.

Our experiments suggest that at low parental virus challenges, offspring exhibit enhanced resistance to the virus, consistent with TGIP. In contrast, at higher parental challenges (i.e. akin to when virus builds up in the host population), the offspring immune system appears to be overwhelmed and the offspring generation becomes more susceptible to viral disease.

This is consistent with what we see in the field, where a ‘typical’ armyworm outbreak season usually comprises low levels of virus early in the season, but higher levels later on – several generations later – perhaps suggesting that TGIP ultimately is not strong enough to mitigate against high levels of horizontal transmission of the virus.

There are potentially a number of biological and environmental factors that may determine whether or not a covert virus is triggered into an overt viral infection, and often laboratory experiments are unable to find consistent triggers: we believe a lot of these factors (environmental and biological) need to align for triggering of covert virus to occur. One theory is that host-challenge by a heterologous (or different) virus can cause the covert virus to be triggered. This has some evolutionary merit. For example, if the covert virus is threatened (i.e. its host may die from another – horizontally transmitted – virus) then it is in its evolutionary interest to ‘escape’ the dying host by killing the host itself and becoming an overt lethal disease capable of horizontal transmission to another susceptible host.

Indeed, in our experiments, we observed when the parents and offspring were challenged with different virus ‘strains’, that as the dose of virus given to the offspring generation increased, so they were much more likely to die from the vertically-transmitted virus strain they inherited from their parents. In other words, when the offspring was challenged by a heterologous virus strain to that of its parent, they were more likely to be killed by a vertically-transmitted ‘covert’ virus that was then ‘triggered’ to become an overt lethal infection as opposed to the virus that it had been challenged with horizontally. We think this is particularly exciting and interesting.

On a broader scale, this could have implications for the sorts of patterns we see of viral outbreaks in natural populations of eruptive caterpillar pests, such as armyworms. Observations in the field seem to suggest particular spatial foci of infection within a population – indicating that maybe something is triggering a covert infection into a full-blown overt disease at a local scale.

There is certainly a lot more to investigate in this area – and a lot of factors to test with regards virus triggering and TGIP. This is a fast-moving area of research aided by the advances in molecular technologies that allow us to investigate microorganisms and their host interactions at a much finer detail.

* Incidentally, Ken’s postdoc work on African armyworms went on to become his first publication in Journal of Animal Ecology [hyperlink to Wilson & Gatehouse 1993] – the armyworm migration has indeed come full circle.

References

Wilson, K. & Gatehouse, A.G. (1993) Seasonal and geographical variation in the migratory potential of outbreak populations of the African armyworm moth, Spodoptera exempta. Journal of Animal Ecology 62: 169-181.

Wilson, K., Grzywacz, D., Cory, J.S., Donkersley, P. & Graham, R.I. (2021) Trans-generational viral transmission and immune priming are dose-dependent. Journal of Animal Ecology (in press)