More than 25 years have passed since the world first woke up to the nightmare of acquired immunodeficiency syndrome and the human immunodeficiency virus that causes it. Over the intervening two-and-a-half decades, according to statistics compiled by the World Health Organization, 25 million people have died. Of those deaths, according to the Centers for Disease Control and Prevention, more than 530,000 were Americans.
Thankfully, these grim statistics are not the full story. Since AIDS was first identified in 1981, important therapeutic breakthroughs have prolonged the lives and reduced the suffering of millions of patients. These treatments, however, are not a cure. Today, an estimated 39.5 million people are living with HIV/AIDS around the globe. Over the next 25 years, according to UN-sponsored research, millions more will contract the disease. As many as 117 million could die.
Scientists such as Marc Johnson, an assistant professor of molecular microbiology and immunology at MU, are determined to avert such a catastrophe. Progress depends, he says, on better understanding how retroviruses, the class of contagion that includes HIV, assemble new viruses.
"What we're working on are ways to better understand and study the process by which viruses, specifically the virus HIV, manufacture new viruses inside infected cells," Johnson says.
Viruses infect healthy cells because they need such cells to reproduce, he explains. "When a healthy cell is compromised, that cell becomes a sort of assembly plant for the production of more virus particles. These particles then leave the cell and seek out new cells to infect, like tiny insidious parasites. So far, much of the research into preventing the spread of HIV has centered on preventing healthy cells from being infected. This is basically trying to stop the virus in a defensive way -- it's only preventing new virus from infecting cells. Comparatively little has been done to see how the virus can be stopped from manufacturing new particles, which would render it incapable of attacking healthy cells in the first place. That's what my research is about."
HIV is a retrovirus, a tiny, RNA-containing organism that infects cells of the human immune system, rendering it susceptible to other infectious diseases. The HIV life cycle goes something like this: The virus enters a human cell and makes DNA copies of its RNA genome using a viral reverse transcriptase enzyme. Such enzymes reverse the typical DNA-to-RNA flow of genetic information; hence the name "retrovirus." The DNA copy of the genome then goes into the nucleus and "hides" inside a host cell's chromosome.
The virus then exploits the host's molecular machinery to make new viral proteins and new viral RNA, which assembles in the cytoplasm of infected cells to form new viruses. These leave the cell, infect new cells, and start the cycle all over again.
Over the last 10 years, scientists have unraveled many of HIV's molecular secrets. They now have a fairly sophisticated understanding of its genes and its proteins, as well as the ways these interact both with each other and with molecules of the host cell. These insights hastened the discovery of the protease inhibitor class of drugs that, when taken in combination with other medicines, can block HIV reproduction and prolong patients' lives.
Nevertheless, Johnson says, there remains a pressing need for new treatments. Not only do the existing drugs come with a bundle of serious side-effects, but HIV's ability to rapidly mutate can quickly make the drugs ineffective. Another problem, he says, is that most drugs attack very late stages of the virus' life cycle, often well after the newly made viruses have begun to attack new cells in the patient.
Published by the Office of Research.
©2007 Curators of the University of Missouri. Click here to contact the editor.