Abstract
Using genome-wide small interfering RNA (siRNA) screens for poliovirus, influenza A virus and rotavirus, we validated the top 6 gene hits PV, RV or IAV to search for host genes that when knocked-down (KD) enhanced virus permissiveness and replication over wild type Vero cells or HEp-2 cells. The enhanced virus replication was tested for 12 viruses and ranged from 2-fold to >1000-fold. There were variations in virus-specific replication (strain differences) across the cell lines examined. Some host genes (CNTD2, COQ9, GCGR, NDUFA9, NEU2, PYCR1, SEC16G, SVOPL, ZFYVE9, and ZNF205) showed that KD resulted in enhanced virus replication. These findings advance platform-enabling vaccine technology, the creation of diagnostic cells substrates, and are informative about the host mechanisms that affect virus replication in mammalian cells.
Highlights
Vero cells, established from an African green monkey are commonly used during poliovirus (PV), rotavirus (RV) and in some influenza A virus (IAV) vaccines [1,2,3,4,5,6,7,8,9,10]
The ability to connect systems biology with host gene discovery to aid our understanding of the virus-host network is essential for creating a universal vaccine cell line
All host genes targeted for KD in Vero cells or HEp-2 cells were !95% silenced before virus infection (Table 2)
Summary
Vero cells, established from an African green monkey (non-human primate; NHP) are commonly used during poliovirus (PV), rotavirus (RV) and in some influenza A virus (IAV) vaccines [1,2,3,4,5,6,7,8,9,10]. Egg-based vaccine production is the current method for vaccines like IAV, but is time-consuming, expensive and cannot respond rapidly to newly emerging strains. Vero cells are being used to make seasonal IAV vaccines due to variants that arise by antigenic drift [12]. Infection with a range of IAVs will promote reassortment of viral segments, leading to a mixture of diverse species, which can be used for vaccination.
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