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 glycoprotein (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 efficiently transduced by MoMLV-based vectors pseudotyped with many different viral 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 nonmammalian cells exhibit blocks at either entry, reverse transcription, or integration. Additionally, VSV-G-pseudotyped MoMLV-based vector transduction is attenuated in the zebrafish cell line ZF4 at entry and/or reverse transcription, whereas other transduction processes are unaffected. We show that the variation of transduction by MoMLV-based vectors in mammalian and nonmammalian cells is not due to differences in culture conditions or cell division rate but is likely the result of divergence in cellular factors required for retroviral transduction.