Fig. 2

Hypothetical host-parasite system where the parasite is adaptively manipulating behaviour via Alpha-1 upregulation in the central nervous system (CNS) of the host. The major known (1, 4, 5) and hypothetical (2, 3) steps required for adaptive behavioural manipulation are presented here. Evidence of steps 2 and 3 has allowed researchers to eliminate the possibility that Alpha-1 upregulation was a side effect of infection. Key: Numbers represent the known and potential fundamental steps in host manipulation: (1) Establishment of parasite in host (location of parasite will vary depending of host-parasite system i.e. CNS, muscle, digestive tract); (2) Source (potentially multiple different sources) of manipulation factors activates at a given time during the parasite's development cycle, releasing manipulation factors into the host; (3) Manipulation factors exert their effects on one or more physiological systems; (4) Molecular change in the host (i.e. Alpha-1 upregulation as in the hypothetical case of Fig. 1) as a result on manipulation factors released by the parasite; (5) Host behavior changes as a result of the molecular change induced by the manipulation factors. Behavioural alteration directly increases the parasite's fitness. Glossary: Manipulative factor: Any molecule/substance released by the parasite that alters the normal functioning of one or more of the major identified pathways for host manipulation, resulting in a molecular shift in the host which ultimately changes the host behavior for the benefit of the parasite; Manipulative factor source: A structure (organelle, membrane, gland, enzyme etc.) which generates manipulative factors for the parasite to use in host manipulation