The Extracellular Molecular Chaperone Clusterin Inhibits Amyloid Fibril Formation and Suppresses Cytotoxicity Associated with Semen-Derived Enhancer of Virus Infection (SEVI)

Abigail K Elias; Mark R Wilson; John A Carver; Ian F Musgrave

doi:10.3390/cells11203259

The Extracellular Molecular Chaperone Clusterin Inhibits Amyloid Fibril Formation and Suppresses Cytotoxicity Associated with Semen-Derived Enhancer of Virus Infection (SEVI)

Cells. 2022 Oct 17;11(20):3259. doi: 10.3390/cells11203259.

Authors

Abigail K Elias^{1

2}, Mark R Wilson^{3

4

5}, John A Carver⁶, Ian F Musgrave⁷

Affiliations

¹ School of Physical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia.
² Department of Hematology, Liverpool Hospital, New South Wales Pathology, Liverpool, NSW 2170, Australia.
³ School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.
⁴ Molecular Horizons Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.
⁵ Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.
⁶ Research School of Chemistry, The Australian National University, Acton, Canberra, ACT 2601, Australia.
⁷ School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia.

Abstract

Clusterin is a glycoprotein present at high concentrations in many extracellular fluids, including semen. Its increased expression accompanies disorders associated with extracellular amyloid fibril accumulation such as Alzheimer's disease. Clusterin is an extracellular molecular chaperone which prevents the misfolding and amorphous and amyloid fibrillar aggregation of a wide variety of unfolding proteins. In semen, amyloid fibrils formed from a 39-amino acid fragment of prostatic acid phosphatase, termed Semen-derived Enhancer of Virus Infection (SEVI), potentiate HIV infectivity. In this study, clusterin potently inhibited the in vitro formation of SEVI fibrils, along with dissociating them. Furthermore, clusterin reduced the toxicity of SEVI to pheochromocytoma-12 cells. In semen, clusterin may play an important role in preventing SEVI amyloid fibril formation, in dissociating SEVI fibrils and in mitigating their enhancement of HIV infection.

Keywords: SEVI; amyloid fibril; clusterin; cytotoxicity; molecular chaperone; protein aggregation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid* / metabolism
Clusterin* / metabolism
HIV Infections* / metabolism
HIV-1* / metabolism
Humans
Peptide Fragments* / metabolism
Protein Tyrosine Phosphatases* / metabolism
Semen / metabolism

Substances

Amyloid
Clusterin
prostatic acid phosphatase (248-286), human
Peptide Fragments
Protein Tyrosine Phosphatases

Grants and funding

This research was funded by a grant (#1068087) to J.A.C. from the National Health and Medical Research Council of Australia.