AIDSWEEKLY Plus; Monday, June 8 & 15, 1998
Daniel J. DeNoon, Senior Editor
The finding provides an explanation for the selective loss of memory T cells during HIV infection. It may also provide clues to the development of an AIDS therapy.
The new data spring from the recent finding that HIV-1 takes advantage of chemokine receptors to infect cells: the CXCR4 receptor for T-cell-tropic viral strains, and the CCR5 receptor for macrophage tropic cells. The natural ligands for these receptors - SDF-1 for CXCR4 and MIP-1(alpha), MIP-1(beta), and RANTES for CCR5 - block HIV infection.
Now University of Tokyo researcher Tatsuo Shioda and colleagues show that the T-cell marker CD26, which is associated with immunologic memory, disables SDF-1 and thus leaves memory T cells particularly vulnerable to HIV infection.
"It can now be speculated that CD26-mediated inactivation of SDF- 1(alpha) and SDF-1(beta) facilitates HIV-1 replication in memory cells rather than in naive cells, and thus contributes at least partly to the preferential loss of memory function in HIV-1 infection," Shioda et al. wrote.
The Japanese research team reported its findings in the Proceedings of the National Academy of Sciences ("Anti-HIV-1 and Chemotactic Activities of Human Stromal Cell-Derived Factor 1(alpha) (SDF-1(alpha)) and SDF-1(beta) Are Abolished by CD26/Dipeptidyl Peptidase IV-Mediated Cleavage," PNAS, 1998;95:6331-6).
Shioda et al. noted that CD26, a leukocyte activation marker, is also known as the enzyme dipeptidyl peptidase IV (DDPIV). Their studies show that CD26 inactivates the normal and anti-HIV activities of the (alpha) and (beta) forms of the chemokine SDF-1.
"These data suggest that CD26-mediated cleavage of SDF-1(alpha) and SDF-1(beta) likely occurs in human bodies and promotes HIV-1 replication and disease progression," they wrote. "It may also explain why memory function of CD4(+) cells is preferentially lost in HIV-1 infection."
The authors suggested that therapeutics based on SDF-1 could be improved by making them resistant to CD26 inactivation.
This work was supported by grants from the Ministry of Education, Science, Sports, and Culture; the Ministry of Health and Welfare; and the Science and Technology Agency of the Japanese government; as well as grants from the Human Science Promotion Foundation and the Organization for Drug ADR Relief, Research, and Development Promotion, and Product Review of Japan.
The corresponding author for this study is Tatsuo Shioda, Department of Infectious Diseases, Institute of Medical Science, University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo 108, Japan. Email: <shioda@ims.u-tokyo.ac.jp>.
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