NEW YORK (Reuters Health) - HIV evades a host’s immune system by producing high levels of CXCR4-binding envelope protein 120 (X4 gp120), which prevents efficient cytotoxic T lymphocyte migration, according to a new study. These findings may lead to new therapeutic approaches to treatment of HIV and other viruses, investigators report in the Journal of Virology for May.
At low concentrations in vitro, X4 gp120 actually attracts CD8 cells and HIV-specific cytotoxic T cells, senior author Dr. Mark C. Poznansky and colleagues found. At higher concentrations, the protein repels the same cells, a phenomenon that Dr. Poznansky’s group calls “fugetaxis.” Target cell expression of X4 gp120 decreased the apoptotic effect of cytotoxic T cells.
Both pertussis toxin and CXCR4-binding antibody inhibited the effect on T-cell migration. Moreover, genetic manipulation of the protein to remove V1 and V2 loops eliminated its repellant property while maintaining T cell attraction. Deleting the V3 loop as well led to a complete loss of the bidirectional cue.
They reproduced these effects in vivo, by sensitizing mice with ovalbumin, then subjecting them to challenge with ovalbumin 3 days later. If the animals were injected with high-dose gp120, but not low doses of the protein, the immune response to the antigen was decreased. However, neither heat-inactivated gp120 nor gp 120 deficient in V loops had any effect on T-cell infiltration after antigen challenge.
“Selective manipulation of chemotactic and fugetactic signals may allow the augmentation of the host immune response,” they write, “thereby providing a novel immunotherapeutic strategy and potentially enhancing vaccine efficacy in the context of HIV-1 infection.”
Such methodology may also be applied to infection with other viruses that encode proteins that affect cell migration, including poxviruses, papillomaviruses and herpes viruses, according to the authors.
Source: J Virol 2004;78:5184-5193. [ Google search on this article ]
MeSH Headings:Antigens, Viral: Chemotaxis, Leukocyte: Immunologic and Biological Factors: Immunologic Factors: Membrane Proteins: Receptors, Cell Surface: Receptors, Immunologic: Receptors, Virus: Retroviridae Proteins: Viral Envelope Proteins: Viral Proteins: HIV Antigens: Viral Structural Proteins: Gene Products, env: HIV Envelope Protein gp120: Receptors, HIV: Receptors, Cytokine: Receptors, Chemokine: Receptors, CXCR4: Chemical Actions and Uses: Chemical Actions: Polyproteins: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
