Years of research have allowed us to conclude how HIV infects cells, but how it causes to immune system to collapse is
still a mystery. There are three main theories that most researchers believe cause the immune system to crash. The first is
that HIV actually destroys immune cells, such as CD4 and CD8 cells. Another is that HIV does not allow new immune cells to
form, and the third is that HIV causes immune cells to redirect their movement which causes self destruction.
David D. Ho of Aaron Diamond AIDS Research Center in New York, and Alan S. Perelson of Los Alamos, New Mexico
calculated that HIV infects and destroys several billion DC4 cells daily. The immune system is not able to keep up the production
of new cells because it can only produce a certain number of new cells. What researchers are hoping to find is an antiretroviral
drug that is able to stop the virus from spreading and destroying immune cells, as well as therapies that can ensure that immune
cells will continue to replicate.
Mike McCune, of Gladstone Institute of Virology and Immunology at the University of California, with the help of
colleagues, compared blood samples of people who were infected with HIV that had not yet received antiretroviral drugs
to HIV infected people who had gone through 12 weeks of antiretroviral drug treatment. They also had a control group of
people who were not infected with HIV. The samples of blood taken from the group who had received the antiretroviral drug
had a higher concentration of CD4 cells than those who had not taken the drug. On the other hand, CD4 cells in those who
had not take the drug survived longer. These observations show that the antiretroviral drug affects the overall amount of CD4
cells by increasing production, not decreasing the destruction of CD4 cells.
In January of 1999 there was a paper published in the Journal of Immunology that stated that HIV seizes a natural immune
process that causes CD4 cells to flood out of the bloodstream and into the lymph nodes. This process is known as homing.
Healthy immune cells flow from the lymph nodes, through tissues, into the blood, and back to the lymph nodes. Their journey is
necessary to patrol the body for invaders. In February of 1997 Miles W. Cloyed at the University of Texas Medical Branch, along
with some colleagues, tested why the journey of the immune cells was being rerouted. They proved, through testing mice, that
when HIV binds to the immune cells the production of protein (CD62L) increases. With the increase of protein the immune cells
head directly to the lymph nodes. Once the HIV command the immune cells to leave their normal flow, thought the blood, they self destruct.
All of the assumptions and research done on how HIV causes the immune system to fail has brought AIDS research closer to
finding a way to help rebuild the immune system, but it has also made researcher realize that with more answers come more questions.
Jack T. Stapleton at the University of Iowa, along with his colleagues
took blood samples from 362 people (mostly caucasian men) that were being
treated for HIV between 1998-2000. The reason for this study was the recent
findings of a potentially beneficial virus, GBV-C. GBV-C is a virus similar
to others that may cause the liver disease Hepatitis. However, GBV-C does
not lead to any known illnesses, instead it might slow the progression of HIV.
The study led by Stapleton showed that there were 144 patients that contracted HIV, as well as GBV-C. Out of those samples, 41 people died by the time the researchers had analyzed the data. On the other hand, out of the 218 patients that only contained the HIV virus, 123 died. Taking into account age, severity of the illness, and type of treatment, patients infected with HIV are four times as likely to survive if they also contain the virus GBV-C, Stapleton suggests.
Another experiment created by the Iowa researches tested the production of HIV cells in test tubes. They infected immune cells with both HIV and GBV-C. The cells containing both viruses produced 30-60% less HIV strands. Through these observations, Stapleton and his research team concluded that GBV-C might cause biological differences to occur, allowing some to be more capable of fighting HIV than others.
David Phipps of Toronto Hospital, and Donald Branch from the Canadian Red Cross Society, found an early detection test for
strands of HIV. Previously, the time between when a person became infected and when HIV was actually detected was anywhere between six
weeks to six months. HIV, because of Phipps and Branch's discovery, can now be detected within 30 minutes of infection.
The researchers decided to focus on the activity of the enzyme, Fyn Kinase, instead of the measuring of antibodies that are produced due to infection. Fyn Kinase is believed to be the initiator of biochemical signals that follow the activation of Tcell antigen receptor on CD4+ and CD8+ T lymphocytes. Phipps and Branch observed Fyn Kinase activity in patients with and without HIV. Those with HIV contained high Fyn Kinase activity and low levels of Fyn protein. They also found that Fyn Kinase activity increases within 30 minutes of infection of the CD4+ T cells. This new-found information revolutionized the way testing for HIV occurs.
The University of Arizona
Biology 181 Honors
Last updated: December 5, 2002
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