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Review
. 2018 Jul 5;54(55):7557-7569.
doi: 10.1039/c8cc01491d.

Structure, function and antagonism of semen amyloids

Annika Röcker  1 , Nadia R Roan, Jay Kant Yadav, Marcus Fändrich, Jan Münch
Affiliations
Review

Structure, function and antagonism of semen amyloids

Annika Röcker et al. Chem Commun (Camb). .

Abstract

Amyloid fibrils are linear polypeptide aggregates with a cross-β structure. These fibrils are best known for their association with neurodegenerative diseases, such as Alzheimer's or Parkinson's, but they may also be used by living organisms as functional units, e.g. in the synthesis of melanin or in the formation of bacterial biofilms. About a decade ago, in a search for semen factors that modulate infection by HIV-1 (a sexually transmitted virus and the causative agent of the acquired immune deficiency syndrome (AIDS)), it was demonstrated that semen harbors amyloid fibrils capable of markedly increasing HIV infection rates. This discovery not only created novel opportunities to prevent sexual HIV-1 transmission but also stimulated research to unravel the natural role of these factors. We discuss here the identification of these intriguing structures, their molecular properties, and their effects on both sexually transmitted diseases and reproductive health. Moreover, we review strategies to antagonize semen amyloid to prevent sexual transmission of viruses.

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Conflict of interest statement

Conflicts of interest

J.M. has out-licensed a patent on the utilization of self-assembling peptides to promote lentiviral gene transfer, which is commercialized under the brand name Protransduzin®. Remaining authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1. TEM image of SEVI fibrils
The scale bar represents 100nm.
Fig. 2
Fig. 2. TEM of a semen sample
Semen from healthy donor contains amyloid fibrils. Scale bar in left panel represents 500 nm, in right panel 200 nm. Reprinted with permission from Springer Nature: Nature communications "Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen." Usmani, Shariq M., et al. 19, Copyright (2014)..
Fig. 3
Fig. 3. Image showing two macrophages that in the presence of semen fibrils have phagocytosed over a dozen spermatozoa
Monocyte-derived macrophages were labeled with the membrane dye Vybrant® DiO (green) while human spermatozoa were labeled with eFluor 670 (red). Image was generated with a Nikon Eclipse Ti-E inverted microscope. Image generated by N. Kohgadai and M. Montano.
Fig. 4
Fig. 4. The molecular tweezer CLR01 acts as a dual-function inhibitor of viral infection featuring both anti-amyloid and antiviral activity
Adapted with permissions from .
Fig. 5
Fig. 5. Hsp104-based treatments that remodel, degrade, or cluster seminal amyloid reduce their ability to stimulate HIV Infection
(A) Electrostatic charge repulsion between the negatively charged surfaces of the viral and target cell membranes. (B) Cationic seminal amyloid fibrils act as “electrostatic bridge” and increase viral attachment and infection. (C). Hsp104 remodels and degrades semen fibrils thereby by antagonizing infection enhancement. (D) Hsp104 promotes the assembly of seminal amyloid into higher-order conglomerates with greatly reduced HIV promoting activity. Reprinted from "Repurposing Hsp104 to antagonize seminal amyloid and counter HIV infection." 22.8, Castellano, Laura M., et al., 1074-1086 94, Copyright (2015), with permission from Elsevier.
See this image and copyright information in PMC

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