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Ribonuclease is partly responsible for the HIV-1 inhibitory effect activated by HLA alloantigen recognition

  1. Author:
    Rugeles, M. T.
    Trubey, C. A.
    Bedoya, V. I.
    Pinto, L. A.
    Oppenheim, J. J.
    Rybak, S. A.
    Shearer, G. M.

  2. Author Address

    NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B-36, Bethesda, MD 20892 USA NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA Univ Antioquia, Medellin, Colombia NCI, SAIC, Lab HPV, Frederick, MD 21701 USA NCI, SAIC, Mol Immunoregulat Lab, Frederick, MD 21701 USA NCI, SAIC, Dev Therapeut Program, Frederick, MD 21701 USA Shearer GM NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B-36, Bethesda, MD 20892 USA
    1. Year: 2003
  2. Journal: Aids
    1. 17
    2. 4
    3. Pages: 481-486
  4. Type of Article: Article
  1. Abstract:

    Objective: This study was performed to determine whether ribonucleases (RNases) contribute to the soluble HIV-1 inhibitory activity that results from the recognition of HLA alloantigens. Design and methods: Supernatants from mixed lymphocyte reactions of peripheral blood mononuclear cells from healthy HLA-discordant individuals exhibited HIV-1 inhibitory activity (alloantigen-stimulated factors; ASF). These supernatants were tested for their sensitivity to heating (90degreesC for 3 min), and for the presence of three RNases belonging to the RNase A superfamily: eosinophil-clerived neurotoxin (EDN); RNase A; and angiogenin. Polyclonal antibodies specific for these RNases were used for Western blot analysis of the ASF, as well as for blocking the HIV-1 inhibitory activity of ASF. In addition, an RNase inhibitor (RI) was used to determine whether the anti-viral activity of ASIF was due to RNase activity. Results: HIV-1 inhibitory activity of ASF was: (i) resistant to heat treatment; (ii) blocked by 58% with an antibody specific for EDN, but not with antibodies against RNase A or angiogenin; and (iii) blocked by 65-100% with an RI. Moreover, Western blot analysis with an anti-EDN antibody detected EDN in the ASF. Conclusion: These findings indicate that the majority of the soluble HIV-1 inhibitory activity contained in the supernatants of mixed lymphocyte reactions is due to EDN or a closely related RNase. (C) 2003 Lippincott Williams Wilkins.

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