AIDS TREATMENT NEWS Issue #384, October 18, 2002
John S. James

On September 26 scientists at the Aaron Diamond AIDS Research Center (ADARC) announced that they had identified a significant contributor to a long-sought antiviral factor, secreted by certain CD8 T-cells, that inhibits HIV replication.(1) This work does not change treatment now, but could lead to the development of a new class of HIV drugs. It was widely reported in the press.

The research team at ADARC, headed by Linqi Zhang, believes that this factor includes three previously known chemicals called alpha defensins. Through various tests, they found that these chemicals were produced by stimulated CD8 cells of three of the long-term non-progressors they are studying (they picked their three best non-progressors among their patients, in order to have the best chance of identifying how their cells are able to keep HIV in check). After the chemicals were identified -- with the help of a protein-chip technology that allows rapid, sensitive testing -- it was found in laboratory tests that antibodies to those chemicals could largely eliminate the anti-HIV activity of those cells -- helping to confirm that an anti-HIV factor is really these three defensins.

Only one to two percent of HIV patients are long-term non- progressors. Since 1986 it has been known that their cells can produce some substance or substances that inhibit HIV.(2) In 1995 it was shown that some of the activity was due to three other chemicals called beta chemokines. But the beta chemokines only block some HIV viruses, those that use the CCR5 receptor on the CD4 cell to enter the cell -- not viruses that use the CXCR4 receptor, which often evolve later in HIV infection.

The defensins are believed to block all HIV, and to act through a completely different mechanism -- possible involving viral transcription, instead of viral entry into the cell. These chemicals have been found not only in long- term non-progressors but in at least some healthy uninfected persons as well, and in several primate species. However they are seldom found in HIV patients who are not non-progressors.

The defensins would be very difficult to use as drugs, if they could be used at all. But when their action is better understood, it may be possible to devise other treatments that have the same effect. Another approach would be to maintain and enhance the body's ability to produce defensins. Either kind of treatment might convert patients into long- term non-progressors who would not become ill despite HIV infection.

References

(1) Zhang L, Yu W, He T and others. Contribution of human alpha-defensin-1, -2, and -3 to the anti-HIV activity of CD8 antiviral factor. SCIENCE EXPRESS. September 26, 2002.

(2) Walker CM, Moody DJ, Stites DP, and Levy JA. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 1986 Dec 19;234(4783):1563-6.

021018
ATN38405

Copyright © 2002 - AIDS Treatment News. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. Subscription lists are kept confidential. AIDS Treatment News, Subscription and Editorial Office: 1233 Locust St., 5th floor Philadelphia, PA 19107 800/TREAT-1-2 toll-free email: aidsnews@critpath.org  http://www.aidsnews.org

Subscription Information: Call 800/TREAT-1-2: Businesses, Institutions, Professionals: $270/year. Includes early delivery of an extra copy by email. Nonprofit organizations: $135/year. Includes early delivery of an extra copy by email. Individuals: $120/year, or $70 for six months. Special discount for persons with financial difficulties: $54/year, or $30 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2002. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2002. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .