Baculovirus-encoded protein BV/ODV-E26 determines tissue tropism and virulence in lepidopteran insects

Lepidopteran nucleopolyhedroviruses (NPVs) show distinct tissue tropism in host insect larvae. However, the molecular mechanism of this tropism is largely unknown. We quantitatively investigated NPV tissue tropism by measuring mRNA levels of viral genes in 16 tissues from Bombyx mori NPV (BmNPV)-infected B. mori larvae and found clear tissue tropism, i.e., BmNPV replicates poorly in the silk glands, midgut, and Malpighian tubule compared with other larval tissues. We next identified the viral genes determining tissue tropism in NPV infection by investigating the phenotypes of larvae infected with 44 BmNPV mutants in which one gene was functionally disrupted by a LacZ cassette insertion. We found that occlusion body (OB) production was markedly enhanced compared with that of the wild type in the middle silk glands (MSGs) of larvae infected with three mutants in which one of three tandemly arrayed genes (Bm7, Bm8, and Bm9) was disrupted. We generated additional mutants in which one or two genes of this gene cluster were partially deleted and showed that Bm8, also known as BV/ODV-E26, was solely required for the suppression of OB production in the MSGs of BmNPV-infected B. mori larvae. Western blotting showed that a LacZ cassette insertion in Bm7 or Bm9 resulted in aberrant expression of Bm8, presumably leading to abnormal OB production in the MSGs. Larval bioassays also revealed that disruption of Bm8 accelerated the death of B. mori larvae. These results suggest that the group I NPV-specific protein BV/ODV-E26 determines tissue tropism and virulence in host lepidopteran insects.