Semen amyloids participate in spermatozoa selection and clearance

Roan, Nadia R.; Sandi-Monroy, Nathallie; Kohgadai, Nargis; Usmani, Shariq M.; Hamil, Katherine G.; Neidleman, Jason; Montaño, Mauricio; Ständker, Ludger; Röcker, Annika; Cavrois, Marielle; Rosen, Jared; Marson, Kara; Smith, James F.; Pilcher, Christopher D.; Gagsteiger, F.; Sakk, Olena; O’Rand, Michael G.; Lishko, Polina V.; Kirchhoff, Frank; Münch, Jan; Greene, Warner C.

doi:10.7554/elife.24888

Cited by 65 publications

(69 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4D). The enhancement of infection of primary monocyte-derived macrophages as well as the striking increases in macropinocytosis observed in this study are reminiscent of a recent report in which clearance of sperm cells by macrophages is suggested to be enhanced by seminal amyloids (55). Parallels between the clearance of spermatocytes by macrophages stimulated to engulf the cells by phagocytosis, and internalization of EBOV by phagocytic cells via a similar uptake mechanism are particularly intriguing.…”

Section: Discussionsupporting

confidence: 83%

Enhancement of Ebola virus infection by seminal amyloid fibrils

Bart

Cohen

Dye

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The 2014 western Africa Ebola virus (EBOV) epidemic was unprecedented in magnitude, infecting over 28,000 and causing over 11,000 deaths. During this outbreak, multiple instances of EBOV sexual transmission were reported, including cases where the infectious individual had recovered from EBOV disease months before transmission. Potential human host factors in EBOV sexual transmission remain unstudied. Several basic seminal amyloids, most notably semen-derived enhancer of viral infection (SEVI), enhance in vitro infection by HIV and several other viruses. To test the ability of these peptides to enhance EBOV infection, viruses bearing the EBOV glycoprotein (EboGP) were preincubated with physiological concentrations of SEVI before infection of physiologically relevant cell lines and primary cells. Preincubation with SEVI significantly increased EboGP-mediated infectivity and replication in epithelium- and monocyte-derived cell lines. This enhancement was dependent upon amyloidogenesis and positive charge, and infection results were observed with both viruses carrying EboGP and authentic EBOV as well as with semen. SEVI enhanced binding of virus to cells and markedly increased its subsequent internalization. SEVI also stimulated uptake of a fluid phase marker by macropinocytosis, a critical mechanism by which cells internalize EBOV. We report a previously unrecognized ability of SEVI and semen to significantly alter viral physical properties critical for transmissibility by increasing the stability of EboGP-bearing recombinant viruses during incubation at elevated temperature and providing resistance to desiccation. Given the potential for EBOV sexual transmission to spark new transmission chains, these findings represent an important interrogation of factors potentially important for this EBOV transmission route.

show abstract

Section: Discussionsupporting

confidence: 83%

Enhancement of Ebola virus infection by seminal amyloid fibrils

Bart

Cohen

Dye

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In some cases, they can even compete with steel in terms of strength (Smith et al 2006). Amyloid fibrils also occur naturally, and thus not only in disease, as they are known to fulfil biological functions such as pigment formation, neuronal signaling, and hormone release (Fowler et al 2007;Maji et al 2009;Roan et al 2011;Roan et al 2017;Rice et al 2019).…”

Section: Small Heat Shock Proteins As Modifiers Of Aggregation-pronementioning

confidence: 99%

Small heat shock proteins in neurodegenerative diseases

Vendredy

Adriaenssens

Timmerman

2020

Cell Stress and Chaperones

View full text Add to dashboard Cite

Small heat shock proteins are ubiquitously expressed chaperones, yet mutations in some of them cause tissue-specific diseases.Here, we will discuss how small heat shock proteins give rise to neurodegenerative disorders themselves while we will also highlight how these proteins can fulfil protective functions in neurodegenerative disorders caused by protein aggregation. The first half of this paper will be focused on how mutations in HSPB1, HSPB3, and HSPB8 are linked to inherited peripheral neuropathies like Charcot-Marie-Tooth (CMT) disease and distal hereditary motor neuropathy (dHMN). The second part of the paper will discuss how small heat shock proteins are linked to neurodegenerative disorders like Alzheimer's, Parkinson's, and Huntington's disease.

show abstract

“…Like other self-assembling AMPs, SEVI fibrils can agglutinate bacteria and promote their phagocytosis (40). Via a similar mechanism, it was demonstrated that SEVI fibrils trap spermatozoa and increase their uptake by macrophages (45). However, the formation of messicle-like species presents a mechanism by which monomeric PAP 248-286 could exert similar biological activities.…”

Section: Discussionmentioning

confidence: 96%

“…Amyloid formed by the PAP 248-286 monomer, known as semen-derived enhancer of viral infection (SEVI), was discovered to be responsible for the large enhancement of HIV infectivity observed in seminal fluid (41). Since its discovery in 2008, SEVI has also been shown to enhance cytomegalovirus, herpes simplex virus type 1 and 2, and ebola virus infection as well as participate in sperm quality control (42–45). The exact mechanism for these activities is still unknown, but it has been hypothesized that the cationic SEVI amyloid can act like a bridge, trapping or bringing cells together (46).…”

Section: Introductionmentioning

confidence: 99%

Rapid formation of peptide/lipid co-aggregates by the amyloidogenic seminal peptide PAP_248-286

Vane

Maibaum

et al. 2020

Preprint

View full text Add to dashboard Cite

5Protein/lipid co-assembly is an understudied phenomenon that is important to the function of antimicrobial peptides as 6 well as the pathological effects of amyloid. Here we study the co-assembly process of PAP 248-286 , a seminal peptide that 7 displays both amyloid-forming and antimicrobial activity. PAP 248-286 is a fragment of prostatic acid phosphatase and has 8 been reported to form amyloid fibrils, known as semen-derived enhancer of viral infection (SEVI), that enhance the viral 9 infectivity of HIV. We find that in addition to forming amyloid, PAP 248-286 much more readily assembles with lipid 10 vesicles into peptide/lipid co-aggregates that resemble amyloid fibrils in some important ways but are a distinct species. 11The formation of these co-aggregates, which we term "messicles", is controlled by the peptide:lipid (P:L) ratio and by the 12 lipid composition. The optimal P:L ratio is around 1:10 and at least 70% anionic lipid is required for co-aggregate 13 formation. Once formed, messicles are not disrupted by subsequent changes in P:L ratio. We propose that messicles form 14 through a polyvalent assembly mechanism, where a critical surface density of PAP 248-286 on liposomes enables peptide-15 mediated particle bridging into larger species. Even at ~100-fold lower PAP 248-286 concentrations, messicles form at least 16 10-fold faster than amyloid fibrils. It is therefore possible that, some or all of the biological activities assigned to SEVI, 17 the amyloid form of PAP 248-286 , could instead be attributed to a PAP 248-286 /lipid co-aggregate. More broadly speaking, this 18 work provides a potential framework for the discovery and characterization of peptide/lipid co-aggregates by other 19 amyloid-forming proteins and antimicrobial peptides. 20 Statement of Significance 21PAP 248-286 , a fragment of prostatic acid phosphatase, forms amyloid thought to enhances the infectivity of many 22 viruses, including HIV. This amyloid, termed semen-derived enhancer of viral infection (SEVI), has been assigned 23 responsibility for all of PAP 248-286 's biological activities, while the monomer is thought to be inactive. However, SEVI 24 formation is quite slow and requires very high concentrations of PAP . Here, we show that PAP 248-286 can instead 25 assemble much more rapidly with lipid membranes to form another species, mechanistically and morphologically distinct 26 from both monomer and SEVI amyloid. We have characterized this new species, which could play a role in the biological 27 activities currently ascribed to SEVI. Additionally, our proposed mechanism for peptide/lipid co-assembly could apply to 28 other biologically important systems. 29 30 Vane et al. PAP 248-286 /lipid co-aggregates 31Protein self-assembly has been important area of study for the past century. It is ubiquitous in biology -essential for 32 normal function and yet also underlying major diseases. Structural filaments like actin and tubulin microtubules, whose 33 assembly is critical for proper cellular motility, morphology, and trans...

show abstract

Semen amyloids participate in spermatozoa selection and clearance

Cited by 65 publications

References 53 publications

Enhancement of Ebola virus infection by seminal amyloid fibrils

Enhancement of Ebola virus infection by seminal amyloid fibrils

Small heat shock proteins in neurodegenerative diseases

Rapid formation of peptide/lipid co-aggregates by the amyloidogenic seminal peptide PAP_248-286

Contact Info

Product

Resources

About

Semen amyloids participate in spermatozoa selection and clearance

Cited by 65 publications

References 53 publications

Enhancement of Ebola virus infection by seminal amyloid fibrils

Enhancement of Ebola virus infection by seminal amyloid fibrils

Small heat shock proteins in neurodegenerative diseases

Rapid formation of peptide/lipid co-aggregates by the amyloidogenic seminal peptide PAP248-286

Contact Info

Product

Resources

About

Rapid formation of peptide/lipid co-aggregates by the amyloidogenic seminal peptide PAP_248-286