Spodoptera exigua microarray was used to determine genes differentially expressed in S. exigua cells challenged with the species-specific baculovirus SeMNPV as well as with a generalist baculovirus, AcMNPV. Microarray results revealed that, in contrast to the host transcriptional shut-off that is expected during baculovirus infection, S. exigua cells showed a balanced number of up- and down-regulated genes during the first 36 hours following the infection. Many immune-related genes, including pattern recognition proteins, genes involved in signalling and immune pathways as well as immune effectors and genes coding for proteins involved in the melanization cascade were found to be down-regulated after baculovirus infection. The down-regulation of immune-related genes was confirmed in the larval gut. The expression of immune-related genes in the gut is known to affect the status of gut microorganisms, many of which are responsible for growth and development functions. We therefore asked whether the down-regulation that occurs after baculovirus infection affects the amount of gut microbiota. An increase in the gut bacterial load was observed and we hypothesize this to be as a consequence of viral infection. Subsequent experiments on virus performance in the presence and absence of gut microbiota revealed that gut bacteria enhanced baculovirus virulence, pathogenicity and dispersion. We discuss the host immune response processes and pathways affected by baculoviruses, as well as the role of gut microbiota in viral infection.