scholarly journals Autographa californica Multiple Nucleopolyhedrovirus GP64 Protein: Roles of Histidine Residues in Triggering Membrane Fusion and Fusion Pore Expansion

2011 ◽  
Vol 85 (23) ◽  
pp. 12492-12504 ◽  
Author(s):  
Z. Li ◽  
G. W. Blissard
Keyword(s):  
Membrane Fusion ◽  
Autographa Californica ◽  
Fusion Pore ◽  
Histidine Residues ◽  
Multiple Nucleopolyhedrovirus ◽  
Autographa Californica Multiple Nucleopolyhedrovirus ◽  
Pore Expansion

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

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Qianlong Yu ◽  
Lisha Bai ◽  
Ning Ji ◽  
Xiaorong Yue ◽  
Yuanyuan Jiang ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Fusion Pore ◽  
Viral Fusion ◽  
Class Iii ◽  
Viral Fusion Protein ◽  
Domain I ◽  
Autographa Californica Multiple Nucleopolyhedrovirus ◽  
Pore Expansion

ABSTRACT 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 its postfusion structure, GP64 is composed of five domains (domains I to V). Domain IV (amino acids [aa] 374 to 407) 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 replace each of the individual residues and the contact-forming residues within domain IV and evaluate their contributions to GP64-mediated membrane fusion and virus infection. In many cases, replacement of a single amino acid had no significant impact on GP64. However, replacement of R392 or disruption of the N381-N385, N384-Y388, N385-W393, or K389-W393 contact resulted in poor cell surface expression and fusion loss of the modified GP64, whereas replacement of E390 or G391 or disruption of the N381-K389, N381-Q401, or N381-I403 contact reduced the cell surface expression level of the constructs and the ability of GP64 to mediate fusion pore expansion. In contrast, replacement of N407 or disruption of contact D404-S406 appeared to restrict fusion pore expansion without affecting expression. Combined with the finding that these constructs remain in the prefusion conformation or have a dramatically less efficient transition from the prefusion to the postfusion state under acidic conditions, we proposed that domain IV is necessary for refolding of GP64 during membrane fusion. IMPORTANCE Baculovirus GP64 is grouped with rhabdovirus G, herpesvirus gB, and thogotovirus glycoproteins as a class III viral fusion protein. In their postfusion structures, these proteins contain five domains (domains I to V). Distinct from domain IV of rhabdovirus G and herpesvirus gB proteins, which is composed of β-sheets, domain IV of GP64 is a loop region; the same domain in thogotovirus glycoproteins 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 highly conserved residues and 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.

The Autographa californica multiple nucleopolyhedrovirus ac110 gene encodes a new per os infectivity factor

2016 ◽  
Vol 221 ◽  
pp. 30-37 ◽  
Author(s):  
Jiantao Liu ◽  
Leyuan Zhu ◽  
Shan Zhang ◽  
Zihao Deng ◽  
Zhihong Huang ◽  
...  
Keyword(s):  
Autographa Californica ◽  
Multiple Nucleopolyhedrovirus ◽  
Autographa Californica Multiple Nucleopolyhedrovirus

scholarly journals Ac102 Participates in Nuclear Actin Polymerization by Modulating BV/ODV-C42 Ubiquitination during Autographa californica Multiple Nucleopolyhedrovirus Infection

2018 ◽  
Vol 92 (12) ◽  
Author(s):  
Yongli Zhang ◽  
Xue Hu ◽  
Jingfang Mu ◽  
Yangyang Hu ◽  
Yuan Zhou ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Proteasomal Degradation ◽  
Autographa Californica ◽  
Host Cells ◽  
Nuclear Accumulation ◽  
Nuclear Actin ◽  
Regulatory Cascade ◽  
Multiple Nucleopolyhedrovirus ◽  
Nucleation Promoting Factor ◽  
Autographa Californica Multiple Nucleopolyhedrovirus

ABSTRACTAs a virus-encoded actin nucleation promoting factor (NPF), P78/83 induces actin polymerization to assist in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) propagation. According to our previous study, although P78/83 actively undergoes ubiquitin-independent proteasomal degradation, AcMNPV encodes budded virus/occlusion derived virus (BV/ODV)-C42 (C42), which allows P78/83 to function as a stable NPF by inhibiting its degradation during viral infection. However, whether there are other viral proteins involved in regulating P78/83-induced actin polymerization has yet to be determined. In this study, we found that Ac102, an essential viral gene product previously reported to play a key role in mediating the nuclear accumulation of actin during AcMNPV infection, is a novel regulator of P78/83-induced actin polymerization. By characterizing anac102knockout bacmid, we demonstrated that Ac102 participates in regulating nuclear actin polymerization as well as the morphogenesis and distribution of capsid structures in the nucleus. These regulatory effects are heavily dependent on an interaction between Ac102 and C42. Further investigation revealed that Ac102 binds to C42 to suppress K48-linked ubiquitination of C42, which decreases C42 proteasomal degradation and consequently allows P78/83 to function as a stable NPF to induce actin polymerization. Thus, Ac102 and C42 form a regulatory cascade to control viral NPF activity, representing a sophisticated mechanism for AcMNPV to orchestrate actin polymerization in both a ubiquitin-dependent and ubiquitin-independent manner.IMPORTANCEActin is one of the most functionally important proteins in eukaryotic cells. Morphologically, actin can be found in two forms: a monomeric form called globular actin (G-actin) and a polymeric form called filamentous actin (F-actin). G-actin can polymerize to form F-actin, and nucleation promoting factor (NPF) is the initiator of this process. Many viral pathogens harness the host actin polymerization machinery to assist in virus propagation. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) induces actin polymerization in host cells. P78/83, a viral NPF, is responsible for this process. Previously, we identified that BV/ODV-C42 (C42) binds to P78/83 and protects it from degradation. In this report, we determined that another viral protein, Ac102, is involved in modulating C42 ubiquitination and, consequently, ensures P78/83 activity as an NPF to initiate actin polymerization. This regulatory cascade represents a novel mechanism by which a virus can harness the cellular actin cytoskeleton to assist in viral propagation.

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