PMID- 31201733 OWN - NLM STAT- MEDLINE DCOM- 20191212 LR - 20200614 IS - 1995-820X (Electronic) IS - 1674-0769 (Print) IS - 1995-820X (Linking) VI - 34 IP - 4 DP - 2019 Aug TI - Improving Baculovirus Transduction of Mammalian Cells by Incorporation of Thogotovirus Glycoproteins. PG - 454-466 LID - 10.1007/s12250-019-00133-0 [doi] AB - Baculovirus can transduce a wide range of mammalian cells and is considered a promising gene therapy vector. However, the low transduction efficiency of baculovirus into many mammalian cells limits its practical application. Co-expressing heterologous viral glycoproteins (GPs), such as vesicular stomatitis virus G protein (VSV G), with baculovirus native envelope protein GP64 is one of the feasible strategies for improving virus transduction. Tick-borne thogotoviruses infect mammals and their GPs share sequence/structure homology and common evolutionary origins with baculovirus GP64. Herein, we tested whether thogotovirus GPs could facilitate the entry of the prototype baculovirus Autographa californica multiple multiple nucleopolyhedrovirus (AcMNPV) into mammalian cells. The gp genes of two thogotoviruses, Thogoto virus and Dhori virus, were inserted into the AcMNPV genome. Both GPs were properly expressed and incorporated into the envelope of the recombinant AcMNPVs. The transduction rates of recombinant AcMNPVs expressing the two thogotovirus GPs increased for approximately 4-12 fold compared to the wild type AcMNPV in six of the 12 tested mammalian cell lines. It seemed that thogotovirus GPs provide the recombinant AcMNPVs with different cell tropisms and showed better performance in several mammalian cells compared to VSV G incorporated AcMNPV. Further studies showed that the improved transduction was a result of augmented virus-endosome fusion and endosome escaping, rather than increased cell binding or internalization. We found the AcMNPV envelope protein GP64-mediated fusion was enhanced by the thogotovirus GPs at relatively higher pH conditions. Therefore, the thogotovirus GPs represent novel candidates to improve baculovirus-based gene delivery vectors. FAU - Hu, Liangbo AU - Hu L AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. AD - University of the Chinese Academy of Sciences, Beijing, 100049, China. FAU - Li, Yimeng AU - Li Y AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. AD - University of the Chinese Academy of Sciences, Beijing, 100049, China. FAU - Deng, Fei AU - Deng F AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. FAU - Hu, Zhihong AU - Hu Z AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. FAU - Wang, Hualin AU - Wang H AUID- ORCID: 0000-0001-8916-4578 AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. h.wang@wh.iov.cn. FAU - Wang, Manli AU - Wang M AUID- ORCID: 0000-0001-8701-3530 AD - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. wangml@wh.iov.cn. LA - eng PT - Journal Article DEP - 20190614 PL - Netherlands TA - Virol Sin JT - Virologica Sinica JID - 101514185 RN - 0 (G protein, vesicular stomatitis virus) RN - 0 (Glycoproteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Recombinant Proteins) RN - 0 (Viral Envelope Proteins) RN - 0 (Viral Fusion Proteins) RN - Autographa californica multiple nuclear polyhedrosis virus SB - IM MH - Animals MH - Baculoviridae/*genetics MH - Cell Line MH - Genetic Vectors MH - Genome, Viral MH - Glycoproteins/*genetics MH - Humans MH - Membrane Glycoproteins/genetics MH - Nucleopolyhedroviruses/physiology MH - Recombinant Proteins/genetics MH - Thogotovirus/*genetics MH - *Transduction, Genetic MH - Viral Envelope Proteins/genetics MH - Viral Fusion Proteins/genetics MH - Viral Tropism MH - *Virus Internalization PMC - PMC6687793 OTO - NOTNLM OT - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) OT - Baculovirus OT - Glycoprotein OT - Mammalian cells OT - Thogotovirus OT - Transduction COIS- The authors declare no competing interests. EDAT- 2019/06/16 06:00 MHDA- 2019/12/18 06:00 PMCR- 2020/06/14 CRDT- 2019/06/16 06:00 PHST- 2019/01/20 00:00 [received] PHST- 2019/04/09 00:00 [accepted] PHST- 2019/06/16 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/06/16 06:00 [entrez] PHST- 2020/06/14 00:00 [pmc-release] AID - 10.1007/s12250-019-00133-0 [pii] AID - 133 [pii] AID - 10.1007/s12250-019-00133-0 [doi] PST - ppublish SO - Virol Sin. 2019 Aug;34(4):454-466. doi: 10.1007/s12250-019-00133-0. Epub 2019 Jun 14.