title: Unraveling the entry mechanism of baculoviruses and its evolutionary implications.
abstract: The entry of baculovirus budded virus into host cells is mediated by two distinct types of envelope fusion proteins (EFPs), GP64 and F protein. Phylogenetic analysis suggested that F proteins were ancestral baculovirus EFPs, whereas GP64 was acquired by progenitor group I alphabaculovirus more recently and may have stimulated the formation of the group I lineage. This study was designed to experimentally recapitulate a possible major step in the evolution of baculoviruses. We demonstrated that the infectivity of an F-null group II alphabaculovirus (Helicoverpa armigera nucleopolyhedrovirus [HearNPV]) can be functionally rescued by coinsertion of GP64 along with the nonfusogenic F(def) (furin site mutated HaF) from HearNPV. Interestingly, HearNPV enters cells by endocytosis and, less efficiently, by direct membrane fusion at low pH. However, this recombinant HearNPV coexpressing F(def) and GP64 mimicked group I virus not only in its EFP composition but also in its abilities to enter host cells via low-pH-triggered direct fusion pathway. Neutralization assays indicated that the nonfusogenic F proteins contribute mainly to binding to susceptible cells, while GP64 contributes to fusion. Coinsertion of GP64 with an F-like protein (Ac23) from group I virus led to efficient rescue of an F-null group II virus. In summary, these recombinant viruses and their entry modes are considered to resemble an evolutionary event of the acquisition of GP64 by an ancestral group I virus and subsequent adaptive inactivation of the original F protein. The study described here provides the first experimental evidence to support the hypothesis of the evolution of baculovirus EFPs.
authors: State Key Laboratory of Virology and Joint Laboratory of Invertebrate Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors: Manli
authors: M
authors: Wang
authors: Jue
authors: J
authors: Wang
authors: Feifei
authors: F
authors: Yin
authors: Ying
authors: Y
authors: Tan
authors: Fei
authors: F
authors: Deng
authors: Xinwen
authors: X
authors: Chen
authors: Johannes A
authors: JA
authors: Jehle
authors: Just M
authors: JM
authors: Vlak
authors: Zhihong
authors: Z
authors: Hu
authors: Hualin
authors: H
authors: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D015726:Giant Cells / Q000821:virology; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D017924:Nucleopolyhedroviruses / Q000472:pathogenicity* / Q000502:physiology*; D010802:Phylogeny; D061987:Sf9 Cells; D018411:Spodoptera; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D017931:DNA Primers; D014760:Viral Fusion Proteins