Toward system-level understanding of baculovirus-host cell interactions: from molecular fundamental studies to large-scale proteomics approaches

Abstract

Baculoviruses are insect viruses extensively exploited as eukaryotic protein expression vectors. Molecular biology studies have provided exciting discoveries on virus-host interactions, but the application of omic high-throughput techniques on the baculovirus-insect cell system has been hampered by the lack of host genome sequencing. While a broader, systems-level analysis of biological responses to infection is urgently needed, recent advances on proteomic studies have yielded new insights on the impact of infection on the host cell. These works are reviewed and critically assessed in the light of current biological knowledge of the molecular biology of baculoviruses and insect cells.

Keywords: apoptosis; baculovirus; cytoskeleton; proteomics; stress response; virus–host interactions.

FIGURE 1

Baculoviral proteins involved in the remodeling of cellular host cytoskeleton. Baculovirus infection induces a reconfiguration of the host cytoskeleton for intracellular traveling of nucleocapsids and virions. Nucleocapsids movement into the nucleus occurs through the F-actin cytoplasmic network. The egress of newly formed virions is dependent on a viral-induced actin polymerization inside the nucleus.

FIGURE 2

Baculovirus subversion of host cellular cycle. Early in infection, the baculovirus causes the augmentation of cellular levels of Cdk1-cyclin B complexes, which are responsible for the regulation of the transition of G2 to M phase. Later on, a viral homolog of host cyclin B, EC27, starts to be expressed and accumulates in the cell. The complex Cdk1-EC27 blocks the cell cycle, and the cells remain arrested In the G2/M phase during the course of infection. Also, EC27 can act in a cyclin D-dependent manner, forming the complex Cdk6-EC27. As a result, the retinoblastoma protein (Rb) becomes phosphorylated, together with the activation of the complex Cdk2-cyclin E. Such phenomena will trigger the components needed for DNA replication, ensuring an environment favorable for viral DNA synthesis and replication.

FIGURE 3

Baculovirus manipulation of host cellular stress response. Successful infection is the result of a compromise between host defense response and inhibition of apoptosis, which creates the perfect environment for the replication of the virus. Pathways in “orange” are viral and in “blue” are from the host.

FIGURE 4

Baculovirus infection impact on host cell metabolism. Baculovirus infection causes an intensification of glycolytic and tricarboxylic acid cycle (TCA) fluxes, which indirectly follows the activation of the PI3K–Akt signaling pathway.