Identification and Characterization of Genes Related to Resistance of Autographa californica Nucleopolyhedrovirus Infection in Bombyx mori

SIMPLE SUMMARY: Autographa californica nucleopolyhedrovirus (AcMNPV) is a kind of baculovirus that was initially found and named for its host, but the previous study reveals several silkworm strains are preferentially susceptible to AcMNPV through intrahemocelical injection method. In the following study, genetics analysis showed that a set of potential genes which controlled resistance of AcMNPV was located on chromosome 3. In the present research, we performed Genome-Wide Association Studies to identify the gene that controls the resistance of AcMNPV, results show that the Niemann-Pick C1 (NPC-1) gene is strongly associated with this resistance. Then we found that there are several amino acid mutations in the protein sequence of BmNPC1 between two different resistance strains of Bombyx mori. RNAi results showed that BmNPC1 successfully suppressed virus infection ability and changed the expression pattern of viral genes. ABSTRACT: In Bombyx mori, as an important economic insect, it was first found that some strains were completely refractory to infection with Autographa californica nucleopolyhedrovirus (AcMNPV) through intrahemocelical injection; whereas almost all natural strains had difficulty resisting Bombyx mori nucleopolyhedrovirus (BmNPV), which is also a member of the family Baculoviridae. Previous genetics analysis research found that this trait was controlled by a potentially corresponding locus on chromosome 3, but the specific gene and mechanism was still unknown. With the help of the massive silkworm strain re-sequencing dataset, we performed the Genome-Wide Association Studies (GWAS) to identify the gene related to the resistance of AcMNPV in this study. The GWAS results showed that the Niemann-Pick type C1 (NPC-1) gene was the most associated with the trait. The knockdown experiments in BmN cells showed that BmNPC1 has a successful virus suppression infection ability. We found a small number of amino acid mutations among different resistant silkworms, which indicates that these mutations contributed to the resistance of AcMNPV. Furthermore, inhibition of the BmNPC1 gene also changed the viral gene expression of the AcMNPV, which is similar to the expression profile in the transcriptome data of p50 and C108 strains.