Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen

Shariq M Usmani; Onofrio Zirafi; Janis A Müller; Nathallie L Sandi-Monroy; Jay K Yadav; Christoph Meier; Tanja Weil; Nadia R Roan; Warner C Greene; Paul Walther; K Peter R Nilsson; Per Hammarström; Ronald Wetzel; Christopher D Pilcher; Friedrich Gagsteiger; Marcus Fändrich; Frank Kirchhoff; Jan Münch

doi:10.1038/ncomms4508

Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen

Nat Commun. 2014 Apr 1:5:3508. doi: 10.1038/ncomms4508.

Authors

Shariq M Usmani¹, Onofrio Zirafi¹, Janis A Müller¹, Nathallie L Sandi-Monroy², Jay K Yadav³, Christoph Meier⁴, Tanja Weil⁴, Nadia R Roan⁵, Warner C Greene⁶, Paul Walther⁷, K Peter R Nilsson⁸, Per Hammarström⁸, Ronald Wetzel⁹, Christopher D Pilcher¹⁰, Friedrich Gagsteiger¹¹, Marcus Fändrich³, Frank Kirchhoff¹, Jan Münch¹

Affiliations

¹ Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
² 1] Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany [2] Kinderwunsch-Zentrum Ulm, 89077 Ulm, Germany.
³ Institute of Pharmaceutical Biotechnology, Ulm University, 89081 Ulm, Germany.
⁴ Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, 89081 Ulm, Germany.
⁵ 1] Department of Urology, University of California, San Francisco, California 94158, USA [2] Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, California 94158, USA.
⁶ 1] Gladstone Institute of Virology and Immunology, University of California at San Francisco, San Francisco, California 94158, USA [2] Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, California 94158, USA.
⁷ Central Electron Microscopy Facility, Ulm University, 89081 Ulm, Germany.
⁸ IFM-Department of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
⁹ Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
¹⁰ HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, California 94158, USA.
¹¹ Kinderwunsch-Zentrum Ulm, 89077 Ulm, Germany.

Abstract

Naturally occurring fragments of the abundant semen proteins prostatic acid phosphatase (PAP) and semenogelins form amyloid fibrils in vitro. These fibrils boost HIV infection and may play a key role in the spread of the AIDS pandemic. However, the presence of amyloid fibrils in semen remained to be demonstrated. Here, we use state of the art confocal and electron microscopy techniques for direct imaging of amyloid fibrils in human ejaculates. We detect amyloid aggregates in all semen samples and find that they partially consist of PAP fragments, interact with HIV particles and increase viral infectivity. Our results establish semen as a body fluid that naturally contains amyloid fibrils that are exploited by HIV to promote its sexual transmission.

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

Acid Phosphatase
Amyloid / metabolism*
Amyloid / ultrastructure
HIV Infections / metabolism*
HIV Infections / virology
HIV-1 / physiology*
Humans
Male
Microscopy, Confocal
Microscopy, Electron, Transmission
Protein Tyrosine Phosphatases / metabolism
Semen / metabolism*
Semen / virology
Seminal Vesicle Secretory Proteins / metabolism

Substances

Amyloid
Seminal Vesicle Secretory Proteins
seminal vesicle-specific antigen
Acid Phosphatase
prostatic acid phosphatase
Protein Tyrosine Phosphatases

Abstract

Publication types

MeSH terms

Substances

Grants and funding