HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages |
| |
Authors: | Freedman Bruce D Liu Qing-Hua Del Corno Manuela Collman Ronald G |
| |
Institution: | (1) Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Room 369E Old Vet Building, 3800 Spruce Street, 19104 Philadelphia, PA;(2) Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA |
| |
Abstract: | The chemokine receptors CCR5 and CXCR4 serve as the cellular receptors in conjunction with CD4 for HIV-1 entry and infection
of target cells. Although the virus has subverted these molecules for its own use, their natural function is to respond to
activation and migration signals delivered by extracellular chemokines. A principal research objective of our laboratory is
to understand the consequences of virus-chemokine receptor interactions for cellular function, as well as for entry and infection.
We hypothesized that CXCR4-using (X4) and CCR5-using (R5) HIV-1 strains might elicit signals through the chemokine receptors
that result in aberrant function and/or regulate virus entry or postentry steps of infection. We have focused on primary human
macrophages, which express both CXCR4 and CCR5, because macrophages are a principal target for HIV-1 in vivo, in appropriate
macrophage activation appears to play a major role in the pathogenesis of certain sequelae of AIDS, such as HIV encephalopathy,
and macrophage infection is regulated at several steps subsequent to entry in ways that are linked to envelope-receptor interactions.
This review summarizes our recent findings regarding the mechanisms of chemokine-receptor signaling in macrophages, the role
of viral envelope glycoproteins in eliciting macrophage signals, and how these activation pathways may participate in macrophage
infection and affect cell functions apart from infection. |
| |
Keywords: | Ion channels CCR5 CXCR4 Calcium AIDS Pyk-2 |
本文献已被 PubMed SpringerLink 等数据库收录! |
|