HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation

Nathaniel Talledge; Huixin Yang; Ke Shi; Raffaele Coray; Guichuan Yu; William G Arndt; Shuyu Meng; Gloria C Baxter; Luiza M Mendonça; Daniel Castaño-Díez; Hideki Aihara; Louis M Mansky; Wei Zhang

doi:10.1016/j.jmb.2023.168143

HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation

J Mol Biol. 2023 Aug 1;435(15):168143. doi: 10.1016/j.jmb.2023.168143. Epub 2023 May 6.

Authors

Nathaniel Talledge¹, Huixin Yang², Ke Shi³, Raffaele Coray⁴, Guichuan Yu⁵, William G Arndt⁶, Shuyu Meng⁷, Gloria C Baxter⁸, Luiza M Mendonça⁹, Daniel Castaño-Díez¹⁰, Hideki Aihara¹¹, Louis M Mansky¹², Wei Zhang¹³

Affiliations

¹ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address: https://twitter.com/BioChemTalledge.
² Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Comparative Molecular Biosciences Graduate Program, University of Minnesota - Twin Cities, St. Paul, MN 55108, USA.
³ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
⁴ BioEM Lab, Biozentrum, University of Basel - Basel, Switzerland.
⁵ Minnesota Supercomputing Institute, Office of the Vice President for Research, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Characterization Facility, College of Sciences and Engineering, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
⁶ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Biochemistry, Molecular Biology and Biophysics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
⁷ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
⁸ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Molecular, Cellular, Developmental Biology, and Genetics Graduate Program, University of Minnesota - Twin Cities, USA.
⁹ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Biochemistry, Molecular Biology and Biophysics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
¹⁰ Instituto Biofisika CSIC-UPV/EHU, Leioa, Bizkaia, Spain.
¹¹ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Biochemistry, Molecular Biology and Biophysics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA.
¹² Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Comparative Molecular Biosciences Graduate Program, University of Minnesota - Twin Cities, St. Paul, MN 55108, USA; Biochemistry, Molecular Biology and Biophysics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address: mansky@umn.edu.
¹³ Institute for Molecular Virology, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA; Characterization Facility, College of Sciences and Engineering, University of Minnesota - Twin Cities, Minneapolis, MN 55455, USA. Electronic address: zhangwei@umn.edu.

PMID: 37150290
PMCID: PMC10524356 (available on 2024-08-01)
DOI: 10.1016/j.jmb.2023.168143

Abstract

Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used the single particle cryo-electron microscopy method to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 Å resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag lattice structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 Å resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10-12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation.

Keywords: cryo-electron microscopy; lentivirus; morphology; retrovirus; virus assembly.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Capsid Proteins / chemistry
Cryoelectron Microscopy
HIV-2* / chemistry
Humans
Virion* / chemistry
Virus Assembly
gag Gene Products, Human Immunodeficiency Virus* / chemistry

Substances

Capsid Proteins
gag Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding