Enhancement of HIV-1 Infectivity by Amyloid Peptides

摘要

Semen-derived enhancer of viral infection (SEVl) is an amyloid material formed from the 248-286 fragment of prostatic acidic phosphatase [PAP(248-286)] that dramatically enhances HIV-1 infectivity [1]. It has been postulated that SEVI, which is highly cationic, increases HIV-1 infectivity by shielding charge repulsion between HIV virions and target cells [2], We tested this hypothesis using non-SEVI amyloid-like fibrils derived from simple peptides of general sequence Ac-K_n(XKXE)_y-NH2 with varying degrees of positive charge appended to the N-terminus [3]. Ac-(XKXE)y"NH2 peptides self-assemble into soluble fibril-like structures with a bilayer architecture; the hydrophobicity of the X residues can be exploited to tune the self-assembly propensity of the resulting sequence [4,5]. We found that cationic Ac-Kn(XKXE)2-NH2 peptides (Figure 1), where X is phenylalanine (Phe) or cyclohexylalanine (Cha), were able to form soluble fibrils that increased HIV-1 infectivity in a SEVI-like manner [3]. The degree to which HIV-1 infectivity was enhanced by these fibrils varied as a function of X and the number of Lys residues appended to the N-terminus. In order to gain additional insight into the varying effects of these materials on HIV-1 infectivity we conducted studies to characterize the equilibrium between monomer and fibril for each of these peptides.