Undergrad Research Summary
Three years of research studying host-pathogen relationships between a virus (baculovirus AcMNPV (Autographa californica nucleopolyhedrovirus)) and its lepidopteran (caterpillar) hosts helicoverpa zea (corn earworm), trichoplusia ni (cabbage looper), heliothis virescens (tobacco budworm). AcMNPV is double stranded DNA virus, and as such, has a relatively large genome (133kb) and contains ~150 genes. Its pathogenesis in susceptible hosts is very interesting as it will infect nearly all of the host tissues, convert ~30% of the host's biomass to viral progeny, and cause the host to liquify into a puddle of virus laden goo. Interesting, hosts in late stages of infection will exert a virus controlled climbing behavior, and start climbing up as high as they can before succumbing to the final stage of infection: liquefaction and release of viral progeny. This may serve the virus and help in its dispersion, or it may help other caterpillars by making infected caterpillars more likely to be eaten by larger predators, birds. In either case, this highlights the incredible biological interactions between hosts and pathogens.
My research in the lab focused on a peculiar aspect of baculoviruses. To spread from host to host, the virus has a specific form called occlusion derived virions (ODV) where the virions are packaged in a protective protein complex (occlusions) in order to survive in the environment (which for a virus is a harsh, cold, dry, high UV light exposure world). Some baculoviruses' ODV contain a single copy of their genome, and some contain multiple copies of their genome. This trait is part of the biology of baculoviruses and is what the "M" (multiple) strands for in AcMNPV.
To become infected, a caterpillar eats virus occlusions on the surface of a plant. When the occlusions pass into the gut of the insect, the high pH (caterpillar guts are basic rather than acidic) causes the protective occlusions to break apart and release ODV. These ODV can then infect gut cells and establish a primary site of infection. Next, the virus moves from these infected gut cells into neighboring tracheal cells (insects' respiratory system is different than humans'). Once these cells are infected in a susceptible host, the infection will become systemic and the virus has won.
The question I was after was why would a virus spend the resource to package multiple copies of its genome in a single infectious particle? An infected cell is an infected cell, regardless if 1 or 10 viral genomes were released during the initial phase of infection. It turns out that in order to establish a systemic infection in its host, the virus was under very strong time-sensitive selection to move from its primary cell of infection (gut cells), to a secondary cell of infection (tracheal cells). If it doesn't make it to the secondary cell fast enough, the primary cell would be eliminated by the caterpillar and the infection lost. The gut cells of many caterpillars get sloughed off in a regular fashion when the insect molts, and eliminated out the back end. By packaging multiple copies of its genome in a single virion, and thus infecting a cell with more than one copy of its genome, the virus can bypass the relatively time-consuming step of replicating its genome. Instead, one of the viral genomes can migrate to the nucleus, take over cellular transcription and translation, and immediately make the proteins necessary to package genomes for cell-to-cell movement (known as budded virus). The other genomes can "wait" in the cytoplasm for these proteins to be synthesized, and appropriately assembled or integrated into the cell's plasma membrane. When ready, these genomes can then be used to make budded virus, infect the secondary site of infection, and go systemic.
My first genome biology paper: Washburn, J. O., Lyons, E. H., Haas-Stapleton, E. J., Volkman, L. E. (1999). Multiple Nucleocapsid Packaging of Autographa californica Nucleopolyhedrovirus Accelerates the Onset of Systemic Infection in Trichoplusia ni. J. Virol. 73: 411-416
