Can Lysozyme be used as an anti-HIV drug?

published: 23 Mar 2007 (1:44)

Currently, there is no effective cure against HIV infection (Human Immunodeficiency Virus). This infection is caused by a retrovirus and can lead to Acquired Immunodeficiency Syndrome (AIDS), a human disease in which the whole immune system fails to recognise any infection and organism became unprotected against any infection and even easiest and most common infections can be fatal. Furthermore, there is no vaccination is available against this virus. HIV infection is now can be considered as a pandemic with total number of infected peoples more than 0.6%

Scientific efforts to stop this infection are failed or very expensive and ineffective and therefore it is very interesting to check, is there any natural mechanisms of antivirus protection can be found in the human organism which will be effective against HIV.

The activity of anti-HIV drug can be assayed in vitro by expression of viral core protein p24 in chronically infected lymphocytes and monocytes. For more information please refer to the original paper [Bourinbaiar and Lee-Huang].

It was shown that during first few months the transmission of HIV-1 from pregnant mother to fetus is very unlikely. This fact was related with the presence of high concentration of chorionic gonadotropin (hCG), hormone crucially important for pregnancy [De Rossi et al, Krivine et al]. As it was shown [Bourinbaiar and Huang, Huang et al.], the the only β-subunit of hCG protein at concentration about 10-100 ng/ml is active against HIV.

Structure of chorionic gonadotropin (hCG) (1HRP) in schematic representation. α- and β-domains are colored green and blue respectively. β-core region (part of the β-domain) colored orange.

hCG protein is a 237 amino acid, 36.7 kDa glycoprotein, which consists from two chains, related with &alpha- and β-subunits. The crystallographic structure was solved at 3.0 angstrom resolution in 1994 [Lapthorn et al.], Protein Data Bank reference code 1HRP. α-subunit is 92 amino acid (colored green) subunit, comprised of 4 β-strands and one short α-helix. This subunit is to Human Follicle Stimulation Hormone (PDB code 1FL7), and surprisingly to the Vammin, a VEGF-F from a snake venom, see for example structures 1WQ8. β-subunit is 145 amino acid (colored blue) subunit, comprised of four β-strands.

Analysis of sequence revealed that the 15 amino acids from the N-terminal of β-core preparation from the urine of pregnant women (dimer of two peptide fragments of β-hCG linked by disulphide bridges, residue numbers 6-40 disulfide bridged to residues 55-92) is identical to human urinary Lysozyme [Huang et al.], also known as human Lysozyme or milk Lysozyme. Further anti-HIV assay revealed, that crude β-core can be fractionated, into three major fractions, Lysozyme with anti-HIV activity, RNases with anti-HIV activity and pure β-core fragment of hCG without anti-HIV activity.

Comparison of anti-HIV activity of human urinary Lysozyme with chicken egg-white Lysozyme reveals that these activities are almost equivalent [Huang et al.]. Despite the presence of such activity it is unclear how it is possible to use Lysozyme in AIDS treatment. The HIV- preventive properties of Lysozyme are also impossible to use due to low effectiveness and furthermore, the mass production is not established yet [Tsuchiya et al.].

Conclusion. , Naturally present Lysozyme expose some anti-HIV activity and in some cases prevents this infection it is impossible to use this protein as a anti-HIV treatment and I (author of Lysozyme.co.uk presume that Lysozyme will never be used as an anti-HIV drug. I'm happy to be wrong.

References

Bourinbaiar, A. S. and Lee-Huang, S. (1995) Anti-HIV effect of beta subunit of human chorionic gonadotropin (βhCG) in vitro. Immunol. Lett. 44, 13-18.
Huang S.L., Huang P.L., Sun Y., Huang Ph.L, Kung H., Blithe D.L. and Chen H.C. (1999). Lysozyme and RNases as anti-HIV components in b-core preparations of human chorionic gonadotropin. Proc.Natl. Acad. Sci. USA. 96. 2678-2681
Krivine, A., Firtion, G., Cao, L., Francoual, C., Henrion, R. & Lebon, P. (1992) HIV replication during the first weeks of life. Lancet 339, 1187-1189.
Lapthorn, A.J., Harris, D.C., Littlejohn, A., Lustbader, J.W., Canfield, R.E., Machin, K.J., Morgan, F.J., Isaacs, N.W. (1994). Crystal structure of human chorionic gonadotropin. Nature 369. 455-461.
De Rossi, A., Ometto, L., Mammano, F., Zanotto, C., Giaquinto, C. and Chieco-Bianchi, L. (1992) Vertical transmission of HIV-1:lack of detectable virus in peripheral blood cells of infected children at birth. AIDS 6, 1117-1120.
Tsuchiya Y., Morioka K., Shirai J. and Yoshida K. (2004) Establishment of a mass production system for human lysozyme as curative medicine to AIDS. Int Conf AIDS. Jul 11-16. 15: abstract no. WePeA5628.

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