Many nonmammalian cells exhibit postentry blocks to transduction by gammaretroviruses pseudotyped with various viral envelopes, including vesicular stomatitis virus G glycoprotein

Previous studies have suggested that Moloney murine leukemia virus (MoMLV)- based vectors pseudotyped with the vesicular stomatitis virus G glycoprotei n (VSV-G) have extensive ability to transduce nonmammalian cells. However, we have identified multiple cell lines from fish (FHM), mosquitoes (Mos-55) , moths (Sf9 and High-5), flies (S2), and frogs (XPK2) that are not efficie ntly transduced by MoMLV-based vectors pseudotyped,vith many different vira l envelope proteins, including VSV-G, while the same vectors are functional in these cells following transfection, A comparison of MoMLV-based vector transduction in mammalian and nonmammalian cells shows that the nonmammalia n cells exhibit blocks at either entry, reverse transcription, or integrati on. Additionally, VSV-G-pseudotyped MoMLV-based vector transduction is atte nuated in the zebrafish cell line ZF4 at entry and/or reverse transcription , whereas other transduction processes are unaffected. We show that the var iation of transduction by MoMLV-based vectors in mammalian and nonmammalian cells is not due to differences in culture conditions or cell division rat e but is likely the result of divergence in cellular factors required for r etroviral transduction.