Postfusion structure of human-infecting Bourbon virus envelope glycoprotein

Bai, C. H.; Qi, Jianxun; Wu, Yan; Wang, Xinjie; Gao, George F.; Peng, Ruchao; Gao, Feng

doi:10.1016/j.jsb.2019.08.005

Cited by 10 publications

(20 citation statements)

References 31 publications

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“…Different from domain IV of herpesviruses gB and VSV G that are made entirely of ␤-sheets, domain IV of GP64 is a loop region in which few residues (amino acids [aa] 394 to 398) have not been solved in the structure (18,24,29,30). Similarly, in thogotovirus (Thogoto virus, Dhori virus, and Bourbon virus) glycoproteins (Gps), domain IV in the postfusion structures has not been solved (23,31). In the prefusion structure of VSV G and a recently determined low-resolution prefusion structure of human cytomegalovirus (HCMV) gB, domain IV is close to domain I (the fusion domain that contains fusion loops) (25,32).…”

mentioning

confidence: 99%

Critical Residues and Contacts within Domain IV of Autographa californica Multiple Nucleopolyhedrovirus GP64 Contribute to Its Refolding during Membrane Fusion

Bai²,

Ji³

et al. 2020

J Virol

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Autographa californica multiple nucleopolyhedrovirus (AcMNPV) GP64 is a class III viral fusion protein that mediates low-pH triggered membrane fusion during virus entry. Although the structure of GP64 in a postfusion conformation has been solved, its prefusion structure and the mechanism of how the protein refolds to execute fusion are unknown. In postfusion structure, GP64 is composed of five domains (domain I-V). Domain IV (374-407 aa) contains two loops (loop 1 and loop 2) that form a hydrophobic pocket at the membrane-distal end of the molecule. To determine the roles of domain IV, we used alanine-scanning mutagenesis to substitute each of the residues and the contacts within domain IV and evaluate their contributions to GP64-mediated membrane fusion and virus infection. In many cases, substitution of a single amino acid has no significant impact on GP64. However, substitution of R392 or disrupting the contact N381-N385, N384-Y388, N385-W393, or K389-W393 resulted in poor cell surface expression and fusion loss of the modified GP64, whereas substitution of E390 or G391, or disrupting the contact N381-K389, N381-Q401, or N381-I403 reduced the cell surface level of the constructs and the ability of GP64 to mediate fusion pore expansion. In contrast, substitution of N407 or disrupting the contact D404-S406 appears to restrict fusion pore expansion without affecting expression. Combined with the identification of these constructs remaining stable prefusion conformation or dramatically less efficient transition from a prefusion to postfusion state under acidic conditions, we proposed that domain IV is necessary for refolding of GP64 during membrane fusion. Importance Baculoviruses GP64 is grouped with rhabdoviruses G, herpesviruses gB, and thogotoviruses glycoproteins as class III viral fusion proteins. In their postfusion structures, these proteins contain five domains (domain I-V). Distinguished from domain IV of rhabdoviruses G and herpesviruses gB that composed of β-sheets, domain IV of GP64 is a loop region and the same domain in thogotovirues glycorproteins has not been solved. In addition, domain IV is proximal to domain I (fusion domain) in prefusion structures of vesicular stomatitis virus (VSV) G and human cytomegalovirus (HCMV) gB but resides at the domain I-distal end of the molecule in a postfusion conformation. In this study, we identified that the highly conserved residues and the contacts within domain IV of AcMNPV GP64 are necessary for low-pH triggered conformational change and fusion pore expansion. Our results highlight the roles of domain IV of class III viral fusion proteins in refolding during membrane fusion.

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mentioning

confidence: 99%

Critical Residues and Contacts within Domain IV of Autographa californica Multiple Nucleopolyhedrovirus GP64 Contribute to Its Refolding during Membrane Fusion

Bai²,

Ji³

et al. 2020

J Virol

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“…Two of these MAbs were able to detect GP expression on cells infected with BRBV. Unfortunately, these antibodies did not neutralize BRBV, suggesting that they do not bind the receptor binding site of the virus ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…BRBV is a negative-sense segmented RNA virus whose genome is composed of 6 gene segments ( 3 ). Segment 4 encodes the viral envelope glycoprotein (GP) that is necessary for virus attachment and entry into cells ( 4 ), and it is the main target for virus-neutralizing antibodies ( 5 ). A total of five human cases of BRBV infection, including two fatal cases, have been reported since the discovery of this virus in 2014.…”

Section: Introductionmentioning

confidence: 99%

Detection of Bourbon Virus-Specific Serum Neutralizing Antibodies in Human Serum in Missouri, USA

Bamunuarachchi

Harastani

Rothlauf

et al. 2022

mSphere

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“…Two of these mAbs were able to detect GP expression on cells infected with BRBV. Unfortunately, these antibodies did not neutralize BRBV, suggesting they do not bind the receptor binding site of the virus [3].…”

Section: Discussionmentioning

confidence: 99%

“…BRBV is a negative-sense segmented RNA virus whose genome is composed of 6 gene segments [2]. Segment 4 encodes the viral envelope glycoprotein (GP) that is necessary for virus attachment and entry into cells [3], and it is the main target for virus neutralizing antibodies [4]. A total of five human BRBV cases, including two fatal cases, have been reported since the discovery of this virus in 2014.…”

Section: Introductionmentioning

confidence: 99%

Detection of Bourbon virus specific serum neutralizing antibodies in human serum in Missouri, USA

Bamunuarachchi

Rothlauf

Harastani

et al. 2022

Preprint

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Bourbon virus (BRBV) was first discovered in 2014 in a fatal human case. Since then it has been detected in the Amblyomma americanum tick in the states of Missouri and Kansas in the United States. Despite the high prevalence of BRBV in ticks in these states, very few human cases have been reported, and the true infection burden of BRBV in the community is unknown. Here, we developed two virus neutralization assays, a VSV-BRBV pseudotyped rapid assay, and a BRBV focus reduction neutralization assay, to assess the seroprevalence of BRBV neutralizing antibodies in human sera collected in 2020 in St. Louis, Missouri. Out of 440 human serum samples tested, three (0.7%) were able to potently neutralize both VSV-BRBV and wild type BRBV. These findings suggest that human infections with BRBV are more common than previously recognized.

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Postfusion structure of human-infecting Bourbon virus envelope glycoprotein

Cited by 10 publications

References 31 publications

Critical Residues and Contacts within Domain IV of Autographa californica Multiple Nucleopolyhedrovirus GP64 Contribute to Its Refolding during Membrane Fusion

Critical Residues and Contacts within Domain IV of Autographa californica Multiple Nucleopolyhedrovirus GP64 Contribute to Its Refolding during Membrane Fusion

Detection of Bourbon Virus-Specific Serum Neutralizing Antibodies in Human Serum in Missouri, USA

Detection of Bourbon virus specific serum neutralizing antibodies in human serum in Missouri, USA

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