Lysozyme and RNases as anti-HIV components in β-core preparations of human chorionic gonadotropin

Lysozyme and RNases as anti-HIV components in β-core preparations of human chorionic gonadotropin

^*Department of Biochemistry, New York University School of Medicine, New York, NY 10016; ^‡Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; ^§Harvard Community Health Plan and Harvard Medical School, Boston, MA 02114; ^¶Laboratory of Biochemical Physiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21701; and ^**Contraception and Reproductive Health Branch, and ^‡‡Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892

Communicated by Bernhard Witkop, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (received for review December 16, 1998)

Abstract

Human chorionic gonadotropin (hCG) preparations contain activity against HIV type 1 (HIV-1). However, there has been controversy about whether some biological activities of hCG β-subunit (hCGβ) preparations are caused by the β-subunit itself or other proteins present in the preparations. We report here the purification, characterization, and identification of three enzymes with anti-HIV activity present in the β-core fraction of hCGβ prepared from the urine of pregnant women. The N-terminal amino acid sequence of one protein is identical to human urinary lysozyme C, and those of the other two are identical to human RNase A and urinary RNase U. We thus refer to these proteins as AVL (antiviral lysozyme) and AVR (antiviral RNases). In addition to HIV-1 inhibition, AVL is capable of lysing Micrococcus lysodeikticus . AVR digests a variety of RNA substrates, including RNA from HIV-1-infected cells. We also find that lysozyme from chicken egg white, human milk, and human neutrophils and RNase A from bovine pancreas possess activity against HIV-1. These findings may offer additional strategies for the treatment of HIV-1 infection.

Footnotes

↵ ‖ Present address: Institute of Molecular Biology, The University of Hong Kong, Hong Kong.
↵ † To whom reprint requests should be addressed. e-mail: sylvia.lee-huang{at}med.nyu.edu or chen{at}helix.nih.gov.
ABBREVIATIONS:

hCG,

human chorionic gonadotropin;

HIV-1,

HIV type 1;

AVL,

antiviral lysozyme;

AVR,

antiviral RNases