Viral- and fungal-mediated behavioral manipulation of hosts: summit disease

Abstract

Summit disease, in which infected hosts seek heights (gravitropism), first noted in modern times by nineteenth-century naturalists, has been shown to be induced by disparate pathogens ranging from viruses to fungi. Infection results in dramatic changes in normal activity patterns, and such parasite manipulation of host behaviors suggests a strong selection for convergent outcomes albeit evolved via widely divergent mechanisms. The two best-studied examples involve a subset of viral and fungal pathogens of insects that induce "summiting" in infected hosts. Summiting presumably functions as a means for increasing the dispersal of the pathogen, thus significantly increasing fitness. Here, we review current advances in our understanding of viral- and fungal-induced summit disease and the host behavioral manipulation involved. Viral genes implicated in this process include a host hormone-targeting ecdysteroid UDP-glucosyltransferase (apparently essential for mediating summit disease induced by some viruses but not all) and a protein tyrosine phosphatase, with light dependance implicated. For summit disease-causing fungi, though much remains obscure, targeting of molting, circadian rhythms, sleep, and responses to light patterns appear involved. Targeting of host neuronal pathways by summit-inducing fungi also appears to involve the production of effector molecules and secondary metabolites that affect host muscular, immune, and/or neurological processes. It is hypothesized that host brain structures, particularly Mushroom Bodies (no relation to the fungus itself), important for olfactory association learning and control of locomotor activity, are critical targets for mediating summiting during infection. This phenomenon expands the diversity of microbial pathogen-interactions and host dynamics. KEY POINTS: • Summit disease or height seeking (gravitropism) results from viral and fungal pathogens manipulating insect host behaviors presumably to increase pathogen dispersal. • Insect baculoviruses and select fungal pathogens exhibit convergent evolution in host behavioral manipulation but use disparate molecular mechanisms. • Targets for affecting host behavior include manipulation of host hormones, feeding, locomotion, and immune, circadian, and neurological pathways.

Keywords: Baculovirus infection; Behavioral manipulation; Entomopathogenic fungi; Host–pathogen interaction; Neurobiological mechanisms; Summit disease.

Fig. 1

Summit disease benefits pathogen transmission. A Baculoviruses primarily infect insects through ingestion (per os), whereas entomopathogenic fungi can infect insects by direct penetration of the cuticle (i.e., topical infection, per cutaneous) and via ingestion. B Examples of fungal infection in different hosts: (1) Entomophthora muscae (Entomophthorales, Entomophthoraceae) infects dipteran insects. Infected flies exhibit a behavior known as summiting (height seeking, gravitropism), ascending to a higher point as the infection progresses. Once the elevated point is reached, the dying fly extends its proboscis, becoming affixed to the substrate via sticky secretions, and then raises its wings. This specific posture facilitates the transmission of the fungus to other potential hosts. Death of the host is timed, with E. muscae typically causing host death at sunset. (2) Ophiocordyceps (Hypocreales, Ophiocordycipitaceae)-ant infection system. After fungal spores infect the ant, Ophiocordyceps hijacks the central nervous system of the ant, causing it to leave its colony, climb vegetation, and attach itself to a leaf or twig in a characteristic “death grip.” The fungus then consumes the ant’s body, using it as a nutrient source. It eventually produces a spore-producing stalk that emerges from the ant’s body, allowing the fungus to release spores into the environment to infect new hosts. (3) Lepidopteran hosts infected with O. sinensis. Insect host nymphs typically burrow and feed underground. Infection results in their displacement upwards to a position a few centimeters below the soil surface. At this point, fungal infection results in death before the host can pupate. The position of the dead cadaver is optimal for the fungal synnema to grow upwards, breaching the soil-air interface to sporulate and complete the fungal life cycle. (4) The fungus Pandora formicae (Entomophthorales, Entomophthoraceae) infects red wood ants (Formica rufa, Linnaeus). Infected ants are often found attached to blades of grass, with a noticeable bundle of fungal rhizoids emerging from the ventral side of their thorax. (5) Grasshoppers (Orthoptera, Latreille) infected with Entomophaga grylli (Entomophthorales, Entomophthoraceae). Infected hosts typically climb to elevated positions, where the fungus grows from the dead cadaver, producing sporulation structures. Summiting aids in the dispersal of fungal spores. Images sourced from Shutterstock and BioRender

Fig. 2

Basic milestones in understanding baculovirus manipulation of insect hosts

Fig. 3

Mechanical processes in host manipulation by facultative (generalist) non-manipulators and specialized behavioral manipulating (“zombie-making”) fungi. Generalists such Metarhizium (Hypocreales, Clavicipitaceae) and Beauveria sp. (Hypocreales, Cordycipitaceae) follow a complete consumption strategy. Entomophthoralean fungi often cause rapid progression of symptoms and manipulation, whereas Hypocrealean fungi (Ophiocordyceps species infect different hosts, such as ants and spiders) exhibit a slower progression. Images: infected Asian long-horned beetle (Anoplophora glabripennis, Motschulsky) with B. bassiana and infected yellow mealworm (Tenebrio molitor, Linnaeus) larvae with Metarhizium (Masoudi et al. 2020)

Fig. 4

Types of summit disease: juvenile and adult, exploiting behaviors of infected insects during periods of quiescence. Image adapted from (Lovett et al. 2020b)

Fig. 5

Simplified potential general mechanism of enhanced insect locomotion through pathogen targeting of mushroom bodies (MBs). Targeting of MBs can alter olfactory association learning and inhibitory signals to the locomotor center, resulting in increased locomotion. The neuroanatomy of the sequence of E. muscae-induced summiting of host flies on a much more refined scale is presented in Elya et al. (2023)