Abstract
BackgroundSemen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP) fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils.Methodology and Principal FindingsHere, we demonstrated that a synthetic 15-residue peptide derived from the HIV-1 gp120 coreceptor-binding region, designated enhancing peptide 2 (EP2), can rapidly self-assemble into nanofibers. These EP2-derivated nanofibers promptly accelerated the formation of semen amyloid fibrils by PAP248-286, as shown by Thioflavin T (ThT) and Congo red assays. The amyloid fibrils presented similar morphology, assessed via transmission electron microscopy (TEM), in the presence or absence of EP2. Circular dichroism (CD) spectroscopy revealed that EP2 accelerates PAP248-286 amyloid fibril formation by promoting the structural transition of PAP248-286 from a random coil into a cross-β-sheet. Newly formed semen amyloid fibrils effectively enhanced HIV-1 infection in TZM-bl cells and U87 cells by promoting the binding of HIV-1 virions to target cells.Conclusions and SignificanceNanofibers composed of EP2 promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection.
Highlights
In 2013, an estimated 35 million people were living with human immunodeficiency virus (HIV) worldwide, and approximately 2.1 million people were newly infected with HIV [1]
Nanofibers composed of enhancing peptide 2 (EP2) promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection
We examined the effect of EP2 on the conversion of PAP248-286 into amyloid fibrils and its potential role in enhancing HIV-1 infection
Summary
In 2013, an estimated 35 million people were living with human immunodeficiency virus (HIV) worldwide, and approximately 2.1 million people were newly infected with HIV [1]. One of the best-characterized seminal amyloid fibrils is SEVI (semen-derived enhancer of virus infection). SEVI fibrils are formed by a peptide derived from residues 248 to 286 of prostatic acid phosphatase (PAP) This peptide, designated PAP248-286, can reportedly enhance the infectious titer of HIV-1 by up to five orders of magnitude [10, 11]. Other PAP fragments (e.g., PAP85-120) and semenogelins (SEM1 and SEM2) promote HIV-1 infection by forming amyloid fibrils in seminal fluid [12,13,14]. Seminal amyloid fibrils are exploited by HIV to promote its infection via sexual transmission. Prostatic acid phosphatase (PAP) fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have been reported to promote the formation of seminal amyloid fibrils
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