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Pericentriolar targeting of the mouse mammary tumor virus GAG protein

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Zhang, Guangzhi, Sharon, David, Jovel, Juan, Liu, Lei, Wine, Eytan, Tahbaz, Nasser, Indik, Stanislav, Mason, Andrew·2015·PLOS ONE
DOI 10.1371/journal.pone.0131515PMC PMC4486188
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Abstract

The Gag protein of the mouse mammary tumor virus (MMTV) is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV), assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A) resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.

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  • Amino acid substitutions in the MA sequence of MPMV, MMTV, JSRV, and spumaviruses relocate their assembly from cytoplasm to plasma membrane, a major shift from type D to type C pattern.

    “The critical role of Gag in virion assembly has been clearly demonstrated by amino acid substitutions(s) in the MA sequence of MPMV, MMTV, JSRV, and spumaviruses, resulting in the relocation of their assembly from cytoplasm to the plasma membrane—a major shift from a type D to a type C pattern”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Zhang et al. 2015

    The Introduction reports that MA mutations redirected M-PMV assembly from the cytoplasm to the plasma membrane, and the Results report plasma-membrane localization of mutant MMTV Gag-GFP. The Discussion reports changed Gag localization after a substitution in foamy virus, but does not specify plasma-membrane assembly; it does not report a comparable substitution in JSRV. The type D-to-type C description appears in the title of an M-PMV study in the References, not as a demonstrated shift for all four viruses. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Zhang, G., Sharon, D., Jovel, J., Liu, L., Wine, E., Tahbaz, N., Indik, S., & Mason, A.
Affiliations
  • University of Alberta (CA)
  • University of Veterinary Medicine Vienna (AT)
Corresponding author
Mason, Andrew
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-06-29
Volume
10
Issue
6
Pages
e0131515
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0131515
PMC
PMC4486188
OpenAlex
W807883059
Cited by
12
References
3
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2017: 2 · 2016: 2
FWCI
0.66
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Alberta Cancer Foundation
  • Canadian Liver Foundation
  • Alberta Innovates
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
mouse mammary tumor virus, Gag protein, matrix protein, YB-1, centrosome maturation, viral capsid assembly, betaretrovirus, Mason-Pfizer monkey virus, centrioles, plasma membrane localization
MeSH terms
Amino Acid Sequence, Animals, Capsid, Centrioles, HeLa Cells, Humans, Mammary Tumor Virus, Mouse, Molecular Sequence Data, Regulatory Sequences, Nucleic Acid, Gene Products, gag, Protein Structure, Tertiary, 5' Untranslated Regions, Green Fluorescent Proteins, Mice, HEK293 Cells

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