Seminal Plasma Factors
Seminal Plasma Factors
Semen, in contrast to other human bodily fluids, contains multiple types of amyloid fibrils under non-diseased conditions. We have demonstrated that these fibrils potently enhance infection by HIV and other sexually transmitted viruses, and characterized the mechanisms by which they do so. We are conducting studies to characterize the physiological function of these fibrils, by assessing how they signal to sperm cells and cells of the female reproductive tract. The effects of seminal plasma components other than semen fibrils are also being characterized both for their effects on HIV infection, reproductive health, as well as to serve as biomarkers of human disease.
The top image shows the ability of semen fibrils (white) to promote HIV infection by facilitating the binding of HIV (red) to cellular targets (blue). Image generated by W. Mothes, J. Luna, and P. Uchil, and used as cover image by Journal of Virology (Roan et al (2009) J Virol 83:73). The bottom image shows electron micrographs of human sperm cells in the absence (left) or presence (right) of semen fibrils. Semen fibrils, in the extracellular space surrounding the sperm cells, directly interact with the sperm membrane (arrows) and affect their activity.
Funding sources for project:
- NIH R00 “Exploring the role of semen amyloids in promoting HIV infection and fertilization” (PI Roan)
- NIH R21 AI116252 “Characterization of gallic acid as a novel HIV microbicide candidate” (PI Roan)
- NIH R21 AI122821 “Characterization of exosomes from semen of uninfected and HIV-infected men” (PI Roan)
- NIH P50 HD055764 “Origins and biological consequences of human infertility” (PI Giudice)"
- NIH R15 GM123447 "Molecular basis of adaptation in seminal proteins of human and other primates" (PI Jensen-Seaman)
- UCSF Department of Urology startup funds
Selected publications related to project:
- Roan N.R., Sandi-Monroy N., Kohgadai N., Usmani S.M., Hamil K.G., Neidleman J., Montano M., Standker L., Rocker A., Cavrois M., Rosen J., Marson K., Smith J.F., Pilcher C.D., Gagsteiger F., Sakk O., O’Rand M., Lishko P.V., Kirchhoff F., Münch J., Greene W.C. Semen amyloids participate in human spermatozoa selection and clearance. 2017. Elife
- LoRicco JG, Xu CS, Neidleman J, Bergkvist M, Greene WC, Roan NR*, Makhatadze GI* (2016) Gallic acid is an antagonist of semen amyloid fibrils that enhance HIV-1 infection. J Biol Chem (*co-corresponding authors)
- Bergman P, Roan NR, Romling U, Bevins CL, Münch J (2016) Amyloid formation: functional friend or fearful foe? J Intern Med
- Usmani SM, Zirafi O, Müller JA, Sandi-Monroy NL, Yadav JK, Meier C, Wil T, Roan NR, Greene WC, Walter P, Nilsson KP, Hammarstrom P, Wetzel R, Pilcher CD, Gagsteiger F, Fandrich M, Kirchhoff F, Münch J (2014) Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen. Nat Commun
- Chen JC, Johnson BA, Erikson DW, Piltonen TT, Barragan F, Chu S, Kohgadai N, Irwin JC, Greene WC, Giudice LC, Roan NR (2014) Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Hum Reprod