Baculovirus induced
pathogenesis and cytoskeletal interactions

Our group studies a virus that infects the larvae of lepidopteran insects (moths/butterflies) called Autographa californica nuclear polyhedrosis virus (AcMNPV). The study of this virus provides an opportunity to contribute to the development of biological alternatives to chemical pesticides, as well as to gain insight into the molecular and cell biology of the target organisms and virus-cell interactions.

AcMNPV is the best-studied member of Baculoviridae, a family of viruses restricted to arthropod hosts. Perhaps because of the strict co-evolution of these viruses with their invertebrate hosts, certain aspects of their replicative strategy are not shared by viruses of vertebrates or plants. For example, baculoviruses use two phenotypes to complete their life cycle in nature. One phenotype, that which is responsible for initiating infection in feeding larvae, is enclosed in a polyhedral-shaped crystalline matrix of protein that serves to protect the virus from the elements. Upon ingestion, the proteinic matrix dissolves very rapidly in the alkaline juices of the insect midgut, freeing the enveloped bacilliform virions to infect differentiating and mature columnar epithelial cells of the midgut. These cells produce primarily the second phenotype, budded virus, which serves to transmit infection throughout the host.

One of the major research efforts in our laboratory is comparing viral pathogenesis in larval insect hosts of varying susceptibilities using a recombinant virus equipped with a reporter gene to track the virus. This approach has yielded valuable information about important benchmarks of the infection process. For example, we have learned that decreasing susceptibility of aging insects is a midgut-related phenomenon; that the midgut is cleared of infection during molting; that the insect's tracheal (respiratory) system, the second tissue infected, is the conduit used by the virus for spreading infection within the host; that within highly susceptible hosts, infection of the tracheal system portends death while in a highly resistant insect, the corn earworm, tracheal infections often are cleared.

To complement our studies in vivo, we study viral pathogenesis and virus-host interactions at the cell and molecular levels as well. These studies primarily are focused on the role of actin, one of the most abundant cellular proteins, in these processes. Actin appears to be involved in viral movement, nucleocapsid morphogenesis, and regulation of the switch from production of one viral phenotype to the other.

(A) An uninfected fifth instar Trichoplusia ni larva. (B) An AcMNPV-infected fifth instar T. Ni larva at the cream-colored stage of pathogenesis. (C) The final stage of pathogenesis of an AcMNPV-infected T. ni larva. Liquefaction.