Enhancement of Ebola virus infection by seminal amyloid fibrils

Significance During the 2014–2016 Ebola outbreak, multiple instances of male-to-female sexual transmission of Ebola virus (EBOV) were reported. While relatively uncommon, EBOV sexual transmission presents a major public health concern, as these transmission events occurred months after recovery. Further, sexual transmission was linked to a resurgence of EBOV disease in Guinea, which had previously been declared Ebola-free. However, the role of host factors involved in sexual transmission remains unknown. We find that seminal amyloids and semen greatly enhance EBOV infection and alter the virion physical properties, stabilizing viral infectivity and protecting the virus from drying. These results promote seminal amyloids as possible targets for intervention to prevent EBOV sexual transmission and seeding new infection chains that reignite an outbreak. 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.