United Press International - Thursday, 23 August 2001
Bruce Sylvester

WASHINGTON, Aug. 23, (UPI) -- Scientists at the National Institute of Mental Health Laboratory of Molecular Biology in Washington, D.C. have found a previously unknown step in the process by which human immunodeficiency virus side-steps bodily barriers, infects human cells, and eventually causes AIDS.

"We knew the disease was bad and we're just finding more evidence of it," Dr. Jon Marsh, co-author of the study with Dr. Yuntao Wu, told United Press International. "The more we know about the things that HIV does that are essential for infection, the more avenues or points of intervention we have. We are still doing basic research on HIV, and the importance of continuing basic research is essential to confronting this virus effectively," said Marsh. He and Dr. Wu are research scientists at the NIMH, a part of the National Institutes of Health.

The results of their research are published in the August 24 issue of Science Magazine.¹

HIV reproduces itself mostly in blood cells called CD4 T cells. T cells are usually in a resting or dormant state. In this state they naturally and effectively resist HIV infection. The NIMH researchers discovered that the HIV virus finds a way to overcome this natural barrier and reproduce within the T cell host.

As a retrovirus, HIV is composed of RNA genetic material, differing from the human cells which are composed of DNA material. After entering a human cell, the HIV RNA creates a DNA copy of itself in order to integrate into the host cell.

The new study shows that after HIV RNA manufactures a DNA copy, but prior to its integration into the cellular DNA, the HIV DNA stimulates the production of viral proteins. These proteins awaken T cells out of their dormant state. Once the T cells are activated, they become vulnerable to invasion by HIV DNA, allowing the virus to integrate into the T Cell DNA structure and replicate within the T cell.

The activation of these proteins and awakening of the T cell from its safe, quiet state is the key step uncovered in this NIMH study.

"So here we see that the virus is even sneakier than we thought," Dr. Richard Sutton, assistant professor of molecular virology and microbiology at Baylor University School of Medicine in Houston told UPI. "Here's a mechanism for it to get into your T cell, which is minding its own business, and then the virus takes command. Once you have an activated T cell you have much higher levels of viral replication."

Dr. Steven E. Hyman, director of the NIMH said, "This work further demonstrates the subtle ways in which HIV avoids the body's natural resistance to infection. Our understanding of these evolved mechanisms better prepares us to attack this deadly virus."

Reference

1. Wu Y, Marsh JW, "Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA", Science 2001 Aug 24;293(5534):1503-1506.

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