Aptamers Against the CD4 Protein Receptor for Inhibition of HIV Infection

The Human Immunodeficiency Virus, which is also known as HIV is a disease that compromises the immune system. Over time – in many cases, a long time – HIV slowly weakens the immune system until AIDS develops (1). AIDS stands for Acquired Immune Deficiency Syndrome. When a person has AIDS, his or her body has been weakened to the point where it is no longer able to effectively fight disease. As a result, many other health problems develop when a person has AIDS (1). HIV and AIDS has become an epidemic in many developing countries around the world and also claimed numerous victims in developed countries such as the United States.

HIV (types 1 and 2) enters susceptible cells either through binding of viral envelope glycoprotein (gp 120) to specific receptors on cell surface, mainly the CD4 molecule itself or through the beta-chemokine receptor-CCR5 (2). Other cells other than the helper T lymphocytes (CD4) such as some B cells, macrophages and glial cells of the central nervous system can also be infected by HIV so long as they bear the CD4 antigen. HIV belongs to a family of RNA viruses called retroviruses; so called because they possess a unique enzyme, reverse transcriptase, used to synthesize virus-specific double-stranded DNA from the viral RNA genome (3). The resultant DNA gets integrated into the genome of the CD4 where it may remain latent for a long time until activated. The DNA then is used as a template for RNA required for HIV production (2).


This immunopathogenic cycle can be prevented by production of a class of structural inhibitor molecules called 'aptamers'. Aptamers are short single‐stranded DNA or RNA sequences that are selected in vitro based on affinity for a target molecule (4). Aptamers also offer advantages over traditional antibody‐based affinity molecules in their ease of production, regeneration and stability; largely due to the chemical properties of nucleic acids versus amino acids. These oligonucleotide sequences have the capacity to recognize virtually any class of target molecules with affinity and specificity (4).With this capability, an attempt will therefore be made to develop aptamers specific to the target protein CD4 which are receptors for the HIV infection. Since HIV has inherently unstable epitopes (antigenic determinants) for antibody to bind to, it is believed that aptamers, known to be more superior inhibitors compared to antibodies could do that more effectively and thus prevent HIV infection.


References:

1. “About HIV and AIDS” AIDS Healthcare Foundation. http://www.aidshealth.org/?gclid=CJnN4orlo6QCFYlY2godJUhT6A. Updated: 2008

2. Chapel, H and Haeney M. Immunodeficiency-Immunopathogenesis of acquired immune deficiency syndrome, In: Essentials of Clinical immunology. London: Blackwell Scientific Publications. 1990:72

3. Okerengwo, A and Anyiwo C E. Immunopathology-The acquired immune deficiency syndrome, In: Essential Immunology. Port Harcourt: Pearl Publishers. 2006: 109-110

4. In Vitro Selection and Characterization of DNA Aptamers Specific for Phospholamban J. Pharmacol. Exp. Ther. (2009) 329(1): 57-63