Review of the Research Report: An Orally Bioavailable, Small Molecule Antagonist of the Chemokine Receptor CCR5, is a Potent Inhibitor of HIV-1 Infection in vitro and in vivo
The human body contains two type of immunity—innate immunity and adaptive immunity. Adaptive immunity provides a specific response against the antigens of pathogens. White blood cells or lymphocytes are the main tools of adaptive immunity. There are two main types of lymphocytes; T and B cells. Pathogens have chemical signals, antigens, which the immune system recognizes. B cells have antibodies that recognize these antigens and kill the pathogens when they are still outside of a cell. T cells have receptors that are antigen specific. They are responsible for attacking pathogens that have already attacked cells. There are two types of T cells. T4 are helper cells that create proteins that grow and develop T cells and B cells. T8 cells are the “killer” cells that actually attack pathogens. T4 cells have 3 receptors on their surface, used for binding with pathogens, CD4 (the main receptor), CXCR4 (the more abundant co-receptor), CCR5 (the less abundant co-receptor).
Viruses are microscopic particles that act like parasitic agents. Viruses reproduce themselves by integrating into the host cell and making viral copies. A virus forms the genetic blueprint for the structure of the Human Immunodeficiency Virus (HIV).
A drawing that shows receptors on HIV
HIV is a retrovirus, which reverses the usual flow of genetic information within the host cell. This allows the virus to reproduce. HIV is both an acute, (symptoms of the disease are seen) and latent (symptoms are not seen) virus. A retrovirus takes viral RNA and transforms it into retroviral DNA. Then the viral DNA enters the host cell?s nucleus and integrates in to the host chromosome. This causes rapid genetic changes within infected people. HIV depletes the T4 cells, which are essential for immunity and antibody production. HIV enters the T4 cells through three receptors: CD4, CXCR4, CCR5.
A drawing of an HIV cell infecting a T4 cell
The infected cells, which contain viral RNA, are lined with envelope proteins that penetrate the lipid bilayer of the cell. Spikes protrude out from the envelop capsule. The spikes consist of gp141 stem and gp120 protein, which is located at the tip of the stem. The protein gp120 on the infected cells binds to the co-receptor CCR5 on the T cells. This allows the virus to become physically closer to the T cells. P24 is an antigen produced in response to HIV infection. Increased levels of P24 show increased levels of virus.
This study tested the ability of SCH-C to inhibit HIV infection in T4 cells. SCH-C is an antagonist, or inhibitor, of the chemokine receptor CCR5 on the T4 cells. SCH-C prevents HIV from entering the T4 cell through the CCR5 receptor. Different methods were used to determine how efficiently SCH-C...