Morphology-Dependent HIV-Enhancing Effect of Semen-Derived Enhancer of Viral Infection

    Authors

    X. Qiao; J. Jeon; A. L. Cole; J. O. Matos; S. Bautista; J. Castillo; I. Hung; Z. H. Gan; S. A. Tatulian; A. M. Cole;B. Chen

    Comments

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    Abbreviated Journal Title

    Biophys. J.

    Keywords

    BETA-AMYLOID FIBRILS; IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEAR-MAGNETIC-RESONANCE; THIOFLAVIN-T BINDING; ACID-PHOSPHATASE; MEDIATED ENHANCEMENT; CHEMICAL-SHIFT; CELL-FREE; SEVI; TRANSMISSION; Biophysics

    Abstract

    PAP248-286 is a 39-residue fragment (residues 248 to 286) derived from protease cleavage of prostatic acidic phosphatase in semen. The amyloid fibrils formed in vitro by PAP248-286 can dramatically enhance human immunodeficiency virus (HIV) infection. To our knowledge, we present the first report that the HIV-enhancing potency of fibrils formed by PAP248-286 is morphology dependent. We identified pleomorphic fibrils by transmission electron microscopy in two buffer conditions. Our solid-state NMR data showed that these fibrils consist of molecules in distinct conformations. In agreement with NMR, fluorescence measurements confirmed that they are assembled along different pathways, with distinct molecular structures. Furthermore, our cell-based infectivity tests detected distinct HIV-enhancing potencies for fibrils in distinct morphologies. In addition, our transmission electron microscopy and NMR results showed that semen-derived enhancer of viral infection fibrils formed in sodium bicarbonate buffer remain stable over time, but semen-derived enhancer of viral infection fibrils formed in phosphate buffered saline keep evolving after the initial 7 days incubation period. Given time, most of the assemblies in phosphate buffered saline will turn into elongated thin fibrils. They have similar secondary structure but different packing than thin fibrils formed initially after 7 days incubation.

    Journal Title

    Biophysical Journal

    Volume

    108

    Issue/Number

    8

    Publication Date

    1-1-2015

    Document Type

    Article

    Language

    English

    First Page

    2028

    Last Page

    2037

    WOS Identifier

    WOS:000353344400021

    ISSN

    0006-3495

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