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Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication

Overview
Journal Front Microbiol
Specialty Microbiology
Date 2019 Aug 24
PMID 31440231
Citations 2
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Abstract

Gag proteins underlie retroviral replication by fulfilling numerous functional roles at various stages during viral life cycle. Out of the four mature proteins, Gag-capsid (CA) is a major component of viral particles, and has been most well studied biogenetically, biochemically and structurally. Gag-CA is composed of two structured domains, and also of a short stretch of disordered and flexible interdomain linker. While the two domains, namely, N-terminal and C-terminal domains (NTD and CTD), have been the central target for Gag research, the linker region connecting the two has been poorly studied. We recently have performed systemic mutational analyses on the Gag-CA linker region of HIV-1 by various experimental and systems. In total, we have demonstrated that the linker region acts as a -modulator to optimize the Gag-related viral replication process. We also have noted, during the course of conducting the research project, that HIV-1 and SIVmac, belonging to distinct primate lentiviral lineages, share a similarly biologically active linker region with each other. In this brief article, we summarize and report the results obtained by mutational studies that are relevant to the functional significance of the interdomain linker of HIV/SIV Gag-CA. Based on this investigation, we discuss about the future directions of the research in this line.

Citing Articles

Human Immunodeficiency Virus Type 2 Capsid Protein Mutagenesis Reveals Amino Acid Residues Important for Virus Particle Assembly.

Yang H, Talledge N, Arndt W, Zhang W, Mansky L J Mol Biol. 2022; 434(19):167753.

PMID: 35868362 PMC: 11057910. DOI: 10.1016/j.jmb.2022.167753.


Mutation in the Disordered Linker Region of Capsid Disrupts Viral Kinetics of a Neuropathogenic SIV in Rhesus Macaques.

Lee C, Hirsch V Microbiol Spectr. 2022; 10(2):e0047822.

PMID: 35297654 PMC: 9045278. DOI: 10.1128/spectrum.00478-22.

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