Evaluation of Immunological Factors in HIV Pathogenesis

Abstract

Since its advent in the 1980s, HIV has created an undisputed havoc for mankind by its intelligence and ability to replicated quickly, develop resistance to host immune factors and utilizing the host machinery for its own use. The virus has infected more than 39.9M people worldwide and although much research has been carried out for its treatment, no cure is available till now. As the virus completely relies on the host machinery, the virus has multiple accessory proteins to counteract the action of host defense mechanisms and evolutionary proteins. Purinergic receptors, P2X have a role in aiding the entry of the HIV to the host cells. As HIV infects the body, extracellular ATP is increased. This ATP increase serves as a means for inducing conformational changes in p2x receptor present on the surface of plasma membrane and allows the virus to enter the host cell. Inhibitors designed for P2X receptors are involved in preventing the virus from entry to host cells. APOBEC3G is a host factor that induces hypermutations into the HIV ssDNA and prevents the virus from successfully replicating, ultimately destroying its structure. However, vif, inhibits the action of apobec3g by recruiting the protein to proteosomal degradation. Tetherin is also a host protein that tethers the virion to the surface of the host plasma membrane. The protein is of unique structure having unique topology and anchors nascent virions to the cell surface using GPI anchors for attachment of the virions. The protein is responsible for inhibiting the virus to escape from the cell without interacting with the viral proteins. Vpu interacts with tetherin and destroys its activity, however, when vpu is absent, tetherin can still act to inhibit the virus. TRIM 5α is pattern recognition protein which recognizes the virus by its capsid protein, prevents the uncoating of the virus and even before reverse transcription, the protein acts to inhibit the virus by its E3 ubiquitinase activity and triggering MAPK pathway.