Full Conversion of the Hemagglutinin-Neuraminidase Specificity of the Parainfluenza Virus 5 Fusion Protein by Replacement of 21 Amino Acids in Its Head Region with Those of the Simian Virus 41 Fusion Protein

Tsurudome, Masato; Nakahashi, Mito; Matsushima, Yoshiaki; Ito, Morihiro; Nishio, Machiko; Kawano, Mitsuo; Komada, Hiroshi; Nosaka, Tetsuya

doi:10.1128/jvi.03549-12

Cited by 7 publications

(19 citation statements)

References 39 publications

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“…In a recent study, using a homology model of the measles virus F protein based on the atomic structure of the prefusion PIV5 F protein (15), residues near the base of the measles virus F model were postulated to be involved in the H interaction (49). Certain measles virus F mutant proteins that were expressed on the surfaces of cells lost the ability to coimmunoprecipitate H protein and were unable to promote fusion, supporting the notion that the mutations were in a region of F that interacts with H. Also, in a separate study, regions of specificity of F proteins involved in HN interaction were identified based on chimeric proteins generated between PIV5 F and simian virus 41 (SV41) F proteins (50,51).…”

mentioning

confidence: 64%

“…Other residues postulated to disrupt measles F-H interactions were located along the base of the measles virus F head model in domain I. Also, in a separate study, switching domain I fragments of PIV5 F with those of SV41 F converted the HN specificity of PIV5 F, resulting in partial triggering of this PIV5-SV41 chimeric F protein by the SV41 HN protein (51). Thus, to probe further the role of domain I of the PIV5 F prefusion structure in HN interaction and fusion promotion, mutations were generated within domain I, near the region of interaction between two protomers.…”

Section: Design Of Single Point Mutations In the Parainfluenza Virus mentioning

confidence: 99%

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Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability

Bose

Heath

Shah

et al. 2013

J Virol

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c Paramyxovirus membrane glycoproteins F (fusion protein) and HN, H, or G (attachment protein) are critical for virus entry, which occurs through fusion of viral and cellular envelopes. The F protein folds into a homotrimeric, metastable prefusion form that can be triggered by the attachment protein to undergo a series of structural rearrangements, ultimately folding into a stable postfusion form. In paramyxovirus-infected cells, the F protein is activated in the Golgi apparatus by cleavage adjacent to a hydrophobic fusion peptide that inserts into the target membrane, eventually bringing the membranes together by F refolding. However, it is not clear how the attachment protein, known as HN in parainfluenza virus 5 (PIV5), interacts with F and triggers F to initiate fusion. To understand the roles of various F protein domains in fusion triggering and metastability, single point mutations were introduced into the PIV5 F protein. By extensive study of F protein cleavage activation, surface expression, and energetics of fusion triggering, we found a role for an immunoglobulin-like (Ig-like) domain, where multiple hydrophobic residues on the PIV5 F protein may mediate F-HN interactions. Additionally, destabilizing mutations of PIV5 F that resulted in HN trigger-independent mutant F proteins were identified in a region along the border of F trimer subunits. The positions of the potential HN-interacting region and the region important for F stability in the lower part of the PIV5 F prefusion structure provide clues to the receptor-binding initiated, HN-mediated F trigger.

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confidence: 64%

Section: Design Of Single Point Mutations In the Parainfluenza Virus mentioning

confidence: 99%

Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability

Bose

Heath

Shah

et al. 2013

J Virol

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“…It is important in this context to note that the HN protein specificity of the F protein also is not solely defined by the primary structure of the F head domain, as we have reported previously (21,31).…”

Section: Discussionmentioning

confidence: 99%

“…We have recently found that a chimeric PIV5 F protein, no. 36, whose 21 amino acids in the head domain are replaced with the SV41 F counterparts, is triggered by the SV41 HN protein but not by the PIV5 HN protein (21). On the other hand, we previously created an SV41 F-specific chimeric HPIV2 HN protein, CH95-571, whose N-terminal 94 residues including the FAR were replaced with the SV41 HN counterparts (10); CH95-571 was renamed SCA for convenience sake in the current study ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin-Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk Domain

Tsurudome

Ito

Ohtsuka

et al. 2015

J Virol

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Virus-specific interaction between the attachment protein (HN) and the fusion protein (F) is prerequisite for the induction of membrane fusion by parainfluenza viruses. This HN-F interaction presumably is mediated by particular amino acids in the HN stalk domain and those in the F head domain. We found in the present study, however, that a simian virus 41 (SV41) F-specific chimeric HPIV2 HN protein, SCA, whose cytoplasmic, transmembrane, and stalk domains were derived from the SV41 HN protein, could not induce cell-cell fusion of BHK-21 cells when coexpressed with an SV41 HN-specific chimeric PIV5 F protein, no. 36. Similarly, a headless form of the SV41 HN protein failed to induce fusion with chimera no. 36, whereas it was able to induce fusion with the SV41 F protein. Interestingly, replacement of 13 amino acids of the SCA head domain, which are located at or around the dimer interface of the head domain, with SV41 HN counterparts resulted in a chimeric HN protein, SCA-RII, which induced fusion with chimera no. 36 but not with the SV41 F protein. More interestingly, retroreplacement of 11 out of the 13 amino acids of SCA-RII with the SCA counterparts resulted in another chimeric HN protein, IM18, which induced fusion either with chimera no. 36 or with the SV41 F protein, similar to the SV41 HN protein. Thus, we conclude that the F protein specificity of the HN protein that is observed in the fusion event is not solely defined by the primary structure of the HN stalk domain. IMPORTANCEIt is appreciated that the HN head domain initially conceals the HN stalk domain but exposes it after the head domain has bound to the receptors, which allows particular amino acids in the stalk domain to interact with the F protein and trigger it to induce fusion. However, other regulatory roles of the HN head domain in the fusion event have been ill defined. We have shown in the current study that removal of the head domain or amino acid substitutions in a particular region of the head domain drastically change the F protein specificity of the HN protein, suggesting that the ability of a given HN protein to interact with an F protein is defined not only by the primary structure of the HN stalk domain but also by its conformation. This notion seems to account for the unidirectional substitutability among rubulavirus HN proteins in triggering noncognate F proteins.T he parainfluenza viruses are classified into the genera Rubulavirus, Avulavirus, and Respirovirus in the family Paramyxoviridae (1, 2). Human parainfluenza virus 1 (HPIV1) and HPIV3 are members of the genus Respirovirus, while HPIV2, HPIV4A, HPIV4B, Simian virus 41 (SV41), and Parainfluenza virus 5 (PIV5) belong to the genus Rubulavirus; Mumps virus (MuV) is not a parainfluenza virus but is a member of the latter genus (1). Newcastle disease virus (NDV) is one of the 10 avian paramyxoviruses of the genus Avulavirus (1). These viruses have two kinds of glycoprotein spikes on the envelope: hemagglutinin-neuraminidase (HN) protein tetramers and fusion (F) protein ...

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Activation of paramyxovirus membrane fusion and virus entry

Jardetzky

Lamb

2014

Current Opinion in Virology

129

145

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The paramyxoviruses represent a diverse virus family responsible for a wide range of human and animal diseases. In contrast to other viruses, such as HIV and influenza virus, which use a single glycoprotein to mediate host receptor binding and virus entry, the paramyxoviruses require two distinct proteins. One of these is an attachment glycoprotein that binds receptor, while the second is a fusion glycoprotein, which undergoes conformational changes that drive virus-cell membrane fusion and virus entry. The details of how receptor binding by one protein activates the second to undergo conformational changes have been poorly understood until recently. Over the past couple of years, structural and functional data have accumulated on representative members of this family, including parainfluenza virus 5, Newcastle disease virus, measles virus, Nipah virus and others, which suggest a mechanistic convergence of activation models. Here we review the data indicating that paramyxovirus attachment glycoproteins shield activating residues within their N-terminal stalk domains, which are then exposed upon receptor binding, leading to the activation of the fusion protein by a ‘provocateur’ mechanism.

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Full Conversion of the Hemagglutinin-Neuraminidase Specificity of the Parainfluenza Virus 5 Fusion Protein by Replacement of 21 Amino Acids in Its Head Region with Those of the Simian Virus 41 Fusion Protein

Cited by 7 publications

References 39 publications

Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability

Mutations in the Parainfluenza Virus 5 Fusion Protein Reveal Domains Important for Fusion Triggering and Metastability

The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin-Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk Domain

Activation of paramyxovirus membrane fusion and virus entry

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