Innate and Acquired Immunity

Rachael French

HIV and Aids Paper

July 13, 2015

Immunodeficiency disorders are a type of disorders that are characterized by “absences, particularly in a single arm of the immune system, that affect the ability of the remaining elements of the body to control their growth.” (Coico, 2009).  The acquired immunodeficiency syndrome known as AIDS is caused by the virus HIV and can be transmitted through sexual contact, sharing of needles, blood transfusions, placental transfer or passage through the birth canal, as well as through breast feeding. Human Immunodeficiency Virus (HIV) is a human retrovirus that infects the cells of the immune system, in particular the T lymphocytes or T cells. HIV attacks these crucial immune response cells, also called CD4+ cells, because HIV uses the protein CD4 present on the surface of the cell to attach itself and ultimately penetrate its way into the living cell. Once HIV is in your body, the virus is able to copy itself over and over, increasing its ability to kill CD4+ T-cells. Soon, infected cells outnumber healthy T-cells; hence, the lower a person’s CD4+ T-cell count goes, the more susceptible the person is to viruses and infections that an otherwise healthy body could fight. In the initial stages of the infection, the decline in T-cell count is gradual. The first few months and years after a person is infected, T-cell counts may remain very near normal or only slightly decreased. It’s when T-cell numbers begin to dip dramatically that patients with HIV begin noticing additional, worsening symptoms of the infection leading to AIDS.

The HIV viral particle contains two strands of identical RNA and three enzymes (integrase, protease, and reverse transcriptase) that make it viable through its life cycle in the human body. HIV enters macrophages and CD4+ T cells by the adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the cell membrane and the release of the HIV capsid into the cell. Entry to the cell begins through interaction of the trimeric envelope complex (gp160 spike) and both CD4 and a chemokine receptor on the cell surface. The first step in fusion involves the high-affinity attachment of the CD4 binding domains of gp120 to CD4. Once gp120 is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine binding domains of gp120 and allowing them to interact with the target chemokine receptor. This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane. The binding and fusion of HIV to a specific type of CD4 receptor and a co-receptor on the surface of the CD4 cell is similar to a key entering a lock. Once unlocked, HIV can fuse with the host cell (CD4 cell) and release its genetic material into the cell. After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell. During reverse transcription, a special enzyme called reverse transcriptase changes the genetic material of the virus, so that it can be integrated into the host cell’s DNA. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow the virus to evade the body's immune system. The single-stranded RNA genome now free from the attached viral proteins begins to copy itself into a complementary DNA (cDNA) molecule. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus. This integration of the viral DNA into the host cell's genome is carried out by the viral enzyme called integrase. The integrated viral DNA may then lie dormant, in the latent stage of HIV infection and remain inactive for several years.