ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation.</p><p><b>METHODS</b>PAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The β sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining.</p><p><b>RESULTS</b>Lactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of β-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion.</p><p><b>CONCLUSION</b>Lactic acid inhibits SEVI fibril formation in vitro.</p>
ABSTRACT
Semen-derived enhancer of viral infection(SEVI) is a peptide fragment (PAP248-286) from prostatic acid phosphatase(PAP), which can enhance human immunodeficiency virus infection. The mechanisms of SEVI include: (1) SEVI with several cationic amino acid residues reduced electrostatic repulsion between HIV virus and the target cells; (2) The disorder state of SEVI in the human body fluids was helpful to the interaction between virus and the target cell membranes; (3) SEVI could capture HIV particles directly and speed the velocity of virus on the surface of the target cells and improve adsorption and fusion. Currently, the substances of inhibiting SEVI activity include: EGCG from green tea, small molecule compound of aminoquinoline Surfen, ThT analogs BTA-EG6. Those compounds might block the combination of HIV and SEVI or prevent the formation of amyloid fibers, and then reduce the enhancement of SEVI. The studies on the biological characteristics and mechanisms of SEVI have a big benefit for the prevention and treatment of HIV infection.
Subject(s)
Humans , Male , HIV Infections , Semen , Physiology , Sexually Transmitted Diseases, Viral , Static ElectricityABSTRACT
The introduction of highly active antiretroviral therapy (HAART) has greatly changed the pattern and natural history of ocular diseases of HIV-infected patients, resulting from the immune recovery and reduction of opportunistic infections. However, ophthalmic complica-tion continues to be concern in AIDS even in the HAART era, especially in developing areas, where absolute majority of HIV-positive patients live. Lack of test facilities and experience, poor conditions of hygiene, different microbiological environment, absence of effective treatment etc., characterize the ophthalmic manifestation of HIV-infected patients in developing countries from that in developed regions and thus pose a great challenge to the ophthalmic treatment in developing area. Not only varied from region to region, ocular complications are distinctive between adults and children. At the same time, the side effects due to the application of HAART pose their own risks of ocular complication and should, therefore, be given more research attention.