New Study Findings Could Lead To New Anti-HIV Drug Therapies
Researchers at the University of Washington could find why the body can not fight against HIV infection. Scientists discovered that during HIV infection is produced a viral protein, called vpu, that interfere directly with the immune system, making it unable to fight infections. Normally, innate immune system helps human body to prevent and to fight infections fight against infections (bacteria, viruses, parasites). HIV, in turn, through various mechanisms manages to trick the immune system, in order to multiply and infect the body.
In AIDS, virus targets and infects CD 4+ lymphocytes, cells that are directly involved in fighting infection. Therefore, AIDS manifestations vary according to the number of CD4 + lymphocytes. Normally, CD4+ lymphocytes number is about 750/microliter. When CD4 + lymphocytes count reaches 200/microliter, human body immunity is severely impaired. It is know that in people infected with HIV, death occurs after infections and cancers that appear due to poor immunity. The most common infections occurring in AIDS include Pneumocystis jiroveci infection, Mycobacterium and Cryptoccocus neoformans. Among cancers, the most common are Kaposi sarcoma and B cell lymphomas.
Human immunodeficiency virus (HIV) is a lentivirus, belonging to the retrovirus family. Like all retroviruses, HIV posses a replication mechanism based on the activity of an enzyme called reverse transcriptase. This enzyme produces DNA copies of the viral genome, which are then inserted into the host cell genome. The virus contains a viral envelope composed of phospholipids in which are embedded host cell proteins and a specific protein called Env, formed of several glycoproteins, such as gp 120 and gp 41. This complex of glycoproteins has a very important role in the attaching process of the virus to the cells that will be infected. HIV genome contains several genes (gag, pol, env, tat, nef, vif, vpu, and rev) that encodes 19 proteins. VPU gene, which encodes vpu protein, is a regulatory gene that coordinate replication and the ability to infect cells.
The study, conducted by researchers from the University of Washington, found that HIV escapes the immune system defenses through viral protein vpu. It seems that viral protein vpu directly interfere with IRF3 (Interferon Regulatory transcription factor), a protein involved in innate immune response. VPU protein binds to this specific protein, thus blocking its action. In this way, HIV manages to escape immune response. This findings have been demonstrated by studies on HIV strains that do not posses vpu protein, being unable to block the immune system response. Researchers hope that by improving protein IRF3 function may improve treatment and prolong survival of patients infected with HIV.
“We have effectively identified a new Achilles heel in the arsenal that HIV uses to overcome the defenses present in the body’s immune system. This knowledge can be used to design new HIV antiviral therapeutics that prevent vpu from interacting with IRF3 and targeting it for destruction, thus enhancing immunity.”, stated Dr. Gale, leader of the study.