AIDSWEEKLY Plus; Monday, August 10 & 17, 1998
Daniel J. DeNoon, Senior Editor
This seeming contradiction provides an answer to the long-standing question of exactly why, when a transmitting individual carries both T-cell-tropic (T-tropic) and macrophage-tropic (M-tropic) HIV strains, only the M-tropic virus is transmitted.
"There really are two effects of Tat," said Kuan-Teh Jeang of the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. "At low concentrations, there is blocking of infectivity. At high concentrations, increased transactivation overrides this inhibition. But that only happens later."
Nearly all infecting HIV-1 strains are M-tropic and require the CCR5 (R5) chemokine receptor for cell entry. The predominance of M- tropic strains continues until just before AIDS appears, when T-tropic strains - which require the CXCR4 (X4) chemokine receptor for cell entry - suddenly take over.
Jeang and colleagues came across unexpected data while exploring co-receptor usage by HIV-1 strains. They found that simple two-amino- acid mutation changes X4-using virus into R5-using virus. This led them to posit that the HIV-1 genome encodes an X4 receptor on R5 virus.
Because the HIV Tat protein is a chemokine-like (or chemokine- antagonist-like) molecule, Jeang et al. tested Tat in a competitive assay and found that it is a selective X4 inhibitor. Tat pretreatment of cells reduces the ability of the cell to respond to SDF-1 (the natural ligand for X4) but not RANTES, MIP-1(alpha), or MIP-1(beta) (the natural ligands for R5).
Jeang noted that a synthetic sequence of nine repetitive arginines has been shown to inhibit X4-using but not R5-using HIV-1.
"Tat goes this one better," he said.
980810
AW980804
Copyright © 1998 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.
Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsfile.com
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 1998. 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, 1998. 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. .