A Degraded Fragment of HIV-1 Gp120 in Rat Hepatocytes Forms Fibrils and Enhances HIV-1 Infection

Abstract

Identification of the host or viral factors that enhance HIV infection is critical for preventing sexual transmission of HIV. Amyloid fibrils derived from human semen, including semen-derived enhancer of virus infection and semenogelins, enhance HIV-1 infection dramatically in vitro. In this study, we reported that a short-degraded peptide fragment 1 (DPF1) derived from native HIV-1 envelope protein gp120-loaded rat hepatocytes, formed fibrils by self-assembly and thus enhanced HIV-1 infection by promoting the binding of HIV-1 to target cells. Furthermore, DPF1-formed fibrils might be used as a crossing seed to accelerate the formation of semen-derived enhancer of virus infection and semenogelin fibrils. It will be helpful to clarify the viral factors that affect HIV-1 infection. DPF1 as an analog of gp120 containing the critical residues for CD4 binding might be useful for designing of HIV vaccines and developing HIV entry inhibitors.

Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

“…It has been reported that the addition of a small amount of preformed SEVI fibrils as seeds to a suspension of soluble PAP248–286 monomers promotes fibril polymerization and eliminates the lag phase for assembly [ 23 , 29 ]. In the present study, myricetin-mediated inhibition of SEVI aggregation seeded by preformed fibrils was determined by the ThT assay.…”

“…PAP257–267 is considered to be the central region of PAP248–286, and this amyloidogenic region of the SEVI precursor peptide PAP248–286 has high fibril-forming propensity. Coincidentally, PAP268–271 has been reported to play an important role in promoting SEVI fibrillation [ 23 ]. Residues G260–N265 are thought to be involved in the initiation of fibrillation [ 40 ], and residues V262–H270 were shown to be the amyloidogenic region for SEVI fibrillation [ 41 ].…”

“…Ten microliters of sample prepared as described above was mixed with 195 μl of ThT working solution (50 μM). The fluorescence of the mixture was measured using an RF-5301 PC spectrofluorophotometer (Shimadzu) at an excitation wavelength of 440 nm and an emission wavelength of 482 nm [ 23 , 52 ].…”

“…The samples were then centrifuged at 12,000 rpm for 5 min, and the red-colored fiber precipitate was dissolved in 50 μl of dimethyl sulfoxide (DMSO). The absorbance of the solution at 490 nm was recorded using an enzyme-linked immunosorbent assay (ELISA) reader (Tecan, Research Triangle Park, NC, USA) [ 23 , 52 ].…”

“…As described above, SEVI is a possible drug target for preventing HIV sexual transmission due to its stable structure and high levels in semen [ 22 ]. The concentration of endogenous SEVI in pooled semen is approximately 35 µg/ml, which considerably exceeds the level (≥ 2 µg/ml) required to enhance infection [ 7 , 23 ]. However, it is not known whether myricetin affects the formation of SEVI amyloid fibrils in semen.…”