On December 6-7, 2007, a national webcast on the evolution of the HIV epidemic will involve the Murray State University campus. This event will be coordinated by both the Howard Hughes Medical Institute and the Office of Undergraduate Research and Scholarly Activities. All sessions will take place in the Applied Science North Building room 304 and will be open to the public. For the informational flyer click here. Below are the brief summaries of the four lectures.
Lecture One 9:00 – 10:00 a.m.
From Outbreak to Epidemic
Bisola O. Ojikutu, M.D., M.P.H.
In 1981, an obscure and deadly disease surfaced. Previously healthy homosexual men in the United States began arriving at clinics with rare cancers and infections usually seen in people with weakened immune systems. Most of them died. The medical community was baffled and the public anxious. As the cases multiplied, so did the questions. Who is at risk? What is causing the disease? Why does it lead to failure of the immune system? And most important: Can it be stopped from spreading? The new disease was named acquired immune deficiency syndrome, or AIDS, and it has now killed more than 25 million people worldwide. After the initial outbreak, different sectors of the public health, medical, scientific, and advocacy communities mobilized in response to the deadly epidemic. They focused on surveillance—that is, detecting and mapping the disease—and prevention.
Lecture Two 10:30 – 11:30 a.m.
AIDS and the HIV Life Cycle
Bruce D. Walker, M.D.
The first AIDS cases—otherwise healthy young men with multiple infections and cancers—were a mystery to even the most seasoned physicians. The symptoms pointed to a major defect in the immune system.
Further investigation found swollen lymph nodes, another sign of immune stress. A clear hypothesis emerged: the cells of the immune system were directly infected. Tissue cultured from patients’ lymph nodes revealed a new virus—a retrovirus. This type of virus contains RNA that it converts to DNA once it infects human cells. Named human immunodeficiency virus, or HIV, its viral code integrates into the host genome, a safe haven from most drugs, and causes lifelong infection. HIV infects lymphocytes throughout the body, disabling the very cells that defend against invading viruses. With a weakened immune system, patients are vulnerable to infections that are normally easy to fend off. A detailed understanding of the HIV life cycle, from cell attachment and entry to translation and assembly of new viruses, can help researchers identify targets for drug therapy.
Lecture Three 9:00 – 10:00 a.m.
Drugs and HIV Evolution
Bisola O. Ojikutu, M.D., M.P.H.
In 1987, four years after HIV was identified, the Food and Drug Administration (FDA) approved the use of azidothymidine (AZT) to slow the progression of HIV infection to full-blown AIDS. AZT targets reverse transcriptase, an enzyme essential to HIV replication in lymphocytes. Unfortunately, HIV evolves rapidly and develops resistance to AZT, making single-drug therapy with reverse transcriptase inhibitors ineffective. In 1996, a new class of antiretroviral drugs, called protease inhibitors, was approved. This development led to a treatment strategy called highly active antiretroviral therapy (HAART), a drug “cocktail” combining multiple drugs that target at least two steps in the HIV life cycle. As a result, deaths from AIDS in developed nations have dropped significantly, making HIV a chronic, treatable disease, not a death sentence. Since 1987, more than 20 drugs have been approved for use in combination to treat HIV infection, and more are in the pipeline. New drug classes include chemical agents that inhibit the virus’s entry into the cell, integration into the host genome, and maturation.
Lecture Four 10:30 – 11:30 a.m.
Vaccines and HIV Evolution
Bruce D. Walker, M.D.
The global HIV epidemic continues to spread: 40 million people are infected worldwide. While drugs are essential in the battle against HIV, a vaccine would be a major advance. A vaccine, for example, can be preventive and does not require frequent dosing. HIV’s ability to evolve rapidly is a major hurdle in developing a vaccine. HIV replication uses a reverse transcriptase enzyme that converts viral RNA into DNA. The enzyme is poor at reading and correcting mistakes. With successive replication cycles, alterations in viral genes accumulate, resulting in the evolution of new viral traits. HIV shows more variability in a single person than the total viral variability seen across a global influenza epidemic. This rapid HIV evolution makes it difficult to pick a stable protein sequence to target for vaccine development. Currently, the focus is on keeping HIV in check rather than developing a completely preventive vaccine. Individuals whose native immunity has kept HIV under control for more than 25 years may provide clues for creating a vaccine.