Human metapneumovirus fusion protein triggering: Increasing complexities by analysis of new HMPV fusion proteins

J. Tyler Kinder; Edita M. Klimyte; Andres Chang; John V. Williams; Rebecca Ellis Dutch

doi:10.1016/j.virol.2019.03.003

Human metapneumovirus fusion protein triggering: Increasing complexities by analysis of new HMPV fusion proteins

J. Tyler Kinder, Edita M. Klimyte, Andres Chang, John V. Williams, Rebecca Ellis Dutch

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

The human metapneumovirus (HMPV) fusion protein (F) mediates fusion of the viral envelope and cellular membranes to establish infection. HMPV F from some, but not all, viral strains promotes fusion only after exposure to low pH. Previous studies have identified several key residues involved in low pH triggering, including H435 and a proposed requirement for glycine at position 294. We analyzed the different levels of fusion activity, protein expression and cleavage of three HMPV F proteins not previously examined. Interestingly, low pH-triggered fusion in the absence of G294 was identified in one F protein, while a novel histidine residue (H434) was identified that enhanced low pH promoted fusion in another. The third F protein failed to promote cell-to-cell fusion, suggesting other requirements for F protein triggering. Our results demonstrate HMPV F triggering is more complex than previously described and suggest a more intricate mechanism for fusion protein function and activation.

Original language	English
Pages (from-to)	248-254
Number of pages	7
Journal	Virology
Volume	531
DOIs	https://doi.org/10.1016/j.virol.2019.03.003
State	Published - May 2019

Bibliographical note

Funding Information:
This work was supported by CCTS TL1 training program (TL1TR000115) and individual NRSA (F30AI114194) to EK, A Great Rivers Affiliate predoctoral fellowship (55710PRE4230022) to AC, and NIAID grant R01AI051517, NIGMS grant P30GM110787, and UK University Research Professor funds to RED. We thank members of the Dutch lab for discussion and evaluation of experiments and the manuscript.

Funding Information:
This work was supported by CCTS TL1 training program ( TL1TR000115 ) and individual NRSA ( F30AI114194 ) to EK, A Great Rivers Affiliate predoctoral fellowship ( 55710PRE4230022 ) to AC , and NIAID grant R01AI051517 , NIGMS grant P30GM110787 , and UK University Research Professor funds to RED .

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

Clade
Fusion
HMPV
Human metapneumovirus
Low pH
Strains
Syncytia

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2019.03.003

Cite this

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title = "Human metapneumovirus fusion protein triggering: Increasing complexities by analysis of new HMPV fusion proteins",

abstract = "The human metapneumovirus (HMPV) fusion protein (F) mediates fusion of the viral envelope and cellular membranes to establish infection. HMPV F from some, but not all, viral strains promotes fusion only after exposure to low pH. Previous studies have identified several key residues involved in low pH triggering, including H435 and a proposed requirement for glycine at position 294. We analyzed the different levels of fusion activity, protein expression and cleavage of three HMPV F proteins not previously examined. Interestingly, low pH-triggered fusion in the absence of G294 was identified in one F protein, while a novel histidine residue (H434) was identified that enhanced low pH promoted fusion in another. The third F protein failed to promote cell-to-cell fusion, suggesting other requirements for F protein triggering. Our results demonstrate HMPV F triggering is more complex than previously described and suggest a more intricate mechanism for fusion protein function and activation.",

keywords = "Clade, Fusion, HMPV, Human metapneumovirus, Low pH, Strains, Syncytia",

author = "Kinder, {J. Tyler} and Klimyte, {Edita M.} and Andres Chang and Williams, {John V.} and Dutch, {Rebecca Ellis}",

note = "Funding Information: This work was supported by CCTS TL1 training program (TL1TR000115) and individual NRSA (F30AI114194) to EK, A Great Rivers Affiliate predoctoral fellowship (55710PRE4230022) to AC, and NIAID grant R01AI051517, NIGMS grant P30GM110787, and UK University Research Professor funds to RED. We thank members of the Dutch lab for discussion and evaluation of experiments and the manuscript. Funding Information: This work was supported by CCTS TL1 training program ( TL1TR000115 ) and individual NRSA ( F30AI114194 ) to EK, A Great Rivers Affiliate predoctoral fellowship ( 55710PRE4230022 ) to AC , and NIAID grant R01AI051517 , NIGMS grant P30GM110787 , and UK University Research Professor funds to RED . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

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language = "English",

volume = "531",

pages = "248--254",

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AU - Klimyte, Edita M.

AU - Chang, Andres

AU - Williams, John V.

AU - Dutch, Rebecca Ellis

N1 - Funding Information: This work was supported by CCTS TL1 training program (TL1TR000115) and individual NRSA (F30AI114194) to EK, A Great Rivers Affiliate predoctoral fellowship (55710PRE4230022) to AC, and NIAID grant R01AI051517, NIGMS grant P30GM110787, and UK University Research Professor funds to RED. We thank members of the Dutch lab for discussion and evaluation of experiments and the manuscript. Funding Information: This work was supported by CCTS TL1 training program ( TL1TR000115 ) and individual NRSA ( F30AI114194 ) to EK, A Great Rivers Affiliate predoctoral fellowship ( 55710PRE4230022 ) to AC , and NIAID grant R01AI051517 , NIGMS grant P30GM110787 , and UK University Research Professor funds to RED . Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/5

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N2 - The human metapneumovirus (HMPV) fusion protein (F) mediates fusion of the viral envelope and cellular membranes to establish infection. HMPV F from some, but not all, viral strains promotes fusion only after exposure to low pH. Previous studies have identified several key residues involved in low pH triggering, including H435 and a proposed requirement for glycine at position 294. We analyzed the different levels of fusion activity, protein expression and cleavage of three HMPV F proteins not previously examined. Interestingly, low pH-triggered fusion in the absence of G294 was identified in one F protein, while a novel histidine residue (H434) was identified that enhanced low pH promoted fusion in another. The third F protein failed to promote cell-to-cell fusion, suggesting other requirements for F protein triggering. Our results demonstrate HMPV F triggering is more complex than previously described and suggest a more intricate mechanism for fusion protein function and activation.

AB - The human metapneumovirus (HMPV) fusion protein (F) mediates fusion of the viral envelope and cellular membranes to establish infection. HMPV F from some, but not all, viral strains promotes fusion only after exposure to low pH. Previous studies have identified several key residues involved in low pH triggering, including H435 and a proposed requirement for glycine at position 294. We analyzed the different levels of fusion activity, protein expression and cleavage of three HMPV F proteins not previously examined. Interestingly, low pH-triggered fusion in the absence of G294 was identified in one F protein, while a novel histidine residue (H434) was identified that enhanced low pH promoted fusion in another. The third F protein failed to promote cell-to-cell fusion, suggesting other requirements for F protein triggering. Our results demonstrate HMPV F triggering is more complex than previously described and suggest a more intricate mechanism for fusion protein function and activation.

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KW - Low pH

KW - Strains

KW - Syncytia

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Human metapneumovirus fusion protein triggering: Increasing complexities by analysis of new HMPV fusion proteins

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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