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J Virol. 2017 Jun 26;91(14). pii: e00298-17. doi: 10.1128/JVI.00298-17. Print 2017 Jul 15.

Disparate Contributions of Human Retrovirus Capsid Subdomains to Gag-Gag Oligomerization, Virus Morphology, and Particle Biogenesis.

Martin JL1,2, Mendonça LM1,3, Angert I1,4, Mueller JD1,4, Zhang W1,3,5, Mansky LM6,2,3,7,8.

Author information

1
Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota, USA.
2
Pharmacology Graduate Program, University of Minnesota, Minneapolis, Minnesota, USA.
3
Division of Basic Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.
4
School of Physics and Astronomy, University of Minnesota, Minneapolis, Minnesota, USA.
5
Characterization Facility, University of Minnesota, Minneapolis, Minnesota, USA.
6
Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota, USA mansky@umn.edu.
7
Department of Microbiology & Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
8
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

The capsid domain (CA) of the retroviral Gag protein is a primary determinant of Gag oligomerization, which is a critical step for immature Gag lattice formation and virus particle budding. Although the human immunodeficiency virus type 1 (HIV-1) CA carboxy-terminal domain (CTD) is essential for CA-CA interactions, the CA CTD has been suggested to be largely dispensable for human T-cell leukemia virus type 1 (HTLV-1) particle biogenesis. To more clearly define the roles of the HTLV-1 CA amino-terminal domain (NTD) and CA CTD in particle biogenesis, we generated and analyzed a panel of Gag proteins with chimeric HIV-1/HTLV-1 CA domains. Subcellular distribution and protein expression levels indicated that Gag proteins with a chimeric HIV-1 CA NTD/HTLV-1 CA CTD did not result in Gag oligomerization regardless of the parent Gag background. Furthermore, chimeric Gag proteins with the HTLV-1 CA NTD produced particles phenotypically similar to HTLV-1 immature particles, highlighting the importance of the HTLV-1 CA NTD in HTLV-1 immature particle morphology. Taken together, these observations support the conclusion that the HTLV-1 CA NTD can functionally replace the HIV-1 CA CTD, but the HIV-1 CA NTD cannot replace the HTLV-1 CA CTD, indicating that the HTLV-1 CA subdomains provide distinct contributions to Gag-Gag oligomerization, particle morphology, and biogenesis. Furthermore, we have shown for the first time that HIV-1 and HTLV-1 Gag domains outside the CA (e.g., matrix and nucleocapsid) impact Gag oligomerization as well as immature particle size and morphology.IMPORTANCE A key aspect in virus replication is virus particle assembly, which is a poorly understood process for most viruses. For retroviruses, the Gag structural protein is the primary driver of virus particle biogenesis, and the CA CTD is the primary determinant of Gag-Gag interactions for HIV-1. In this study, the HTLV-1 capsid amino-terminal domain was found to provide distinct contributions to Gag-Gag oligomerization, particle morphology, and biogenesis. This study provides information that will aid efforts for discovery of therapeutic targets for intervention.

KEYWORDS:

Gag; morphology; oligomerization; retrovirus; virus assembly

PMID:
28446667
PMCID:
PMC5487576
DOI:
10.1128/JVI.00298-17
[Indexed for MEDLINE]
Free PMC Article

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