Baculovirus transduction in mammalian cells is affected by the production of type I and III IFNs, which is mainly mediated by the cGAS-STING pathway

BEVACQUA, ROMINA; ALFONSO, VICTORIA; MOLINA, GUIDO; TABOGA, OSCAR; AMALFI, SABRINA; LÓPEZ, MARÍA GABRIELA

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2020 vol. 94

0022-538X

The baculovirus Autographa californica multiple nucleopolyhedrovirus is an insect virus with a circular double-stranded DNA genome, which, among other multiple biotechnological applications, is used as an expression vector for gene delivery in mammalian cells. Nevertheless, the nonspecific immune response triggered by viral vectors often suppresses transgene expression. To understand the mechanisms involved in that response, in the present study, we studied the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by using two approaches: the genetic edition through CRISPR/Cas9 technology of genes encoding STING or cGAS in NIH/3T3 murine fibroblasts and the infection of human epithelial cells HEK293 and HEK293 T, deficient in cGAS or in cGAS and STING expression, respectively. Overall, our results suggest the existence of two different pathways involved in the establishment of the antiviral response, both dependent on STING expression. Particularly, the cGAS-STING pathway resulted more relevant in the production of interferon (IFN)-β and IFN-λ1 in response to baculovirus infection. In human epithelial cells, IFN-λ1 production was also induced in a cGAS-independent and DNA-PK-dependent manner. Finally, we demonstrated that these cellular responses towards baculovirus infection affect the efficiency of transduction of baculovirus vectors.