HIV Shows Ability To Infect A Second Major Class Of Immune Cell
COLUMBUS, Ohio - HIV, the virus that causes AIDS, can evolve the ability to infect a second major class of immune-system cells late in the course of the disease, new research shows.
Previously, HIV was thought to infect mainly a type of immune cell known as helper T lymphocytes, or CD4 lymphocytes. This new research suggests that after HIV is in the body for a time, it develops the ability to infect a second major class of immune cells known as CD8 lymphocytes.
"This has important implications for any therapies under development that are designed to block HIV by preventing its binding to the CD4 receptor or to the co-receptor."
The finding, published in the January issue of Nature Medicine with an accompanying editorial, is based on HIV strains isolated from a single patient. But if the work is verified, and if the phenomenon occurs widely, it might help explain why people infected with HIV develop AIDS. It might also provide a way to slow or prevent the development of AIDS.
"This finding is based on a single patient," said Kunal Saha, principal author of the paper and assistant professor of molecular virology, immunology, and medical genetics and of pediatrics at Ohio State.
"The important question now is whether this is a rare phenomenon or a common occurrence," said Saha, who also holds an appointment at Children's Hospital in Columbus. "If it is a common occurrence, then it is a real problem."
And a source of hope.
"If the destruction of CD8 lymphocytes by HIV is why people develop AIDS, perhaps we now have a chance to stop the advance of the disease. Perhaps we can develop a vaccine to block these evolved viruses from attacking CD8 lymphocytes and prolong the lives of people infected with HIV."
CD8 lymphocytes play an important role in fighting viral infections, including HIV infection. For example, they actively destroy HIV during the 10 years or more that can pass between when an individual becomes infected and when they develop AIDS.
Evidence until now has indicated that HIV uses the CD4 receptor, plus a co-receptor, to enter and infect cells. Only certain cells have this receptor, and the most important of these is the CD4 lymphocyte.
CD4 lymphocytes are the cells most hard-hit by HIV. A person infected with HIV can live for 10 or 15 years or even longer with few signs of illness. During this time, the immune system is waging war with HIV and the number of CD4 lymphocytes gradually declines until all or nearly all are destroyed.
Eventually the majority of infected people develop AIDS, although this can often be forestalled through the use of anti-AIDS drug therapy.
The development of AIDS also involves a drop in numbers of CD8 lymphocytes as the disease progresses, but the cause of the drop is not understood.
Examples of HIV infecting CD8 T cells have been reported in people with AIDS but these examples were thought to be unimportant in the development of AIDS.
Researchers believed such cells became infected early in their development. This can happen because immature CD8 lymphocytes briefly display both CD4 and CD8 receptors. The cells lose the CD4 receptors as they mature.
The evidence presented by Saha and a team of researchers is the first to suggest that HIV might acquire the ability to infect mature CD8 lymphocytes.
Furthermore, their work has shown that the HIV they isolated retains the ability to infect CD4 lymphocytes.
Last, the researchers learned that the isolated viruses infect CD8 lymphocytes using the CD8 receptor only; that is, without need of the commonly used co-receptors.
This has important implications for any therapies under development that are designed to block HIV by preventing its binding to the CD4 receptor or to the co-receptor. Such drugs would probably be ineffective against HIV that can attack CD8 lymphocytes.
Saha's research was funded by grants from the National Institutes of Health and the American Foundation for AIDS Research (AmFAR).
# Contact: Kunal Saha, (614) 722-2683sahak@pediatrics.ohio-state.edu Written by Darrell E. Ward, (614) 292-8456; Ward.25@osu.edu