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Viruses. 2018 Aug 28;10(9). pii: E460. doi: 10.3390/v10090460.

Classical Swine Fever Virus p7 Protein Interacts with Host Protein CAMLG and Regulates Calcium Permeability at the Endoplasmic Reticulum.

Author information

1
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Douglas.Gladue@ars.usda.gov.
2
Biofisika Institute, University of the Basque Country (CSIC-UPV/EHU), 48940 Leioa, Spain. eneko.largo@gmail.com.
3
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Lauren.Holinka-patterson@jax.org.
4
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Elizabeth.Ramirez@ars.usda.gov.
5
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA. Elizabeth.Ramirez@ars.usda.gov.
6
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Elizabeth.Vuono2@ars.usda.gov.
7
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA. Elizabeth.Vuono2@ars.usda.gov.
8
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. keithab@princeton.edu.
9
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, USA. keithab@princeton.edu.
10
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA. Guillermo.Risatti@uconn.edu.
11
Biofisika Institute, University of the Basque Country (CSIC-UPV/EHU), 48940 Leioa, Spain. joseluis.nieva@ehu.eus.
12
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Manuel.Borca@ars.usda.gov.

Abstract

We have previously shown that Classical Swine Fever Virus (CSFV) p7 is an essential nonstructural protein with a viroporin activity, a critical function in the progression of virus infection. We also identified p7 domains and amino acid residues critical for pore formation. Here, we describe how p7 specifically interacts with host protein CAMLG, an integral ER transmembrane protein involved in intracellular calcium release regulation and signal response generation. Detection of interaction as well as the identification of p7 areas mediating interaction with CAMLG was performed by yeast two-hybrid. p7-CAMLG interaction was further confirmed by confocal microscopy in eukaryotic cells, co-expressing both proteins. Mutant forms of p7 having substituted native residues identified as mediating interaction with CAMLG showed a decreased co-localization compared with the native forms of p7. Furthermore, it is shown that native p7, but not the mutated forms of p7 that fail to interact with CAMLG, efficiently mediates calcium permeability in the ER. Interestingly, viruses harboring some of those mutated forms of p7 have been previously shown to have a significantly decreased virulence in swine.

KEYWORDS:

CAMLG; CSF; CSFV; classical swine fever; viroporin

PMID:
30154321
PMCID:
PMC6165257
DOI:
10.3390/v10090460
[Indexed for MEDLINE]
Free PMC Article

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