Insane in the brain: How a virus manipulates a caterpillar’s brain function and behavior to enhance transmission.

Manipulation of host behavior is a common strategy exploited by parasites to increase transmission. Although exquisite examples of such behavioral alterations are known, the underlying mechanisms are poorly understood. Baculoviruses, which are viruses specifically infecting insects, provide a unique system to study these mechanisms. Baculoviruses induce hyperactivity (enhanced locomotion activity) and tree-top disease (climbing to elevated positions prior to death) in caterpillars. It was discovered that a viral gene encoding a protein tyrosine phosphatase (PTP) is inducing hyperactivity in baculovirus-infected Spodoptera exigua larvae, and that the phosphatase activity of the PTP protein is important for this behavioral change. With this proposal, we aim to identify the pathway(s) activated by the baculovirus ptp gene that eventually lead(s) to hyperactive host behavior. Since locomotion is primarily controlled by the central nervous system, we will focus on the brain of the infected caterpillars. We will (1) identify the (viral or host) substrate(s) of PTP, (2) identify differentially expressed genes linked to the expression of ptp, (3) study which neural pathways are activated in the host brain by ptp, and (4) perform a detailed analysis of the role of (viral and/or host) genes and proteins identified in aim 1-3 in hyperactive host behavior. This approach will reveal the signal transduction pathways that respond to PTP, leading to altered brain activity and ultimately a change in host locomotion.