Antiviral potential of chemokines

Abstract

In the past few years, a large number of new chemokines (chemotactic cytokines) and chemokine receptors have been discovered. The growth in knowledge about these molecules has been achieved largely through advances in bioinformatics and the expansion of expression sequence tag (EST) databases. It is now clear that chemokines are crucial in controlling both the development and functioning of leukocytes and that their role is not restricted to cell attraction, as originally assumed. In particular, recent findings provide strong support for the idea that chemokines and their receptors are especially important in the control of viral infection and replication. Thus, specific chemokines are now known to enhance the cytotoxic activity of infected cells, thus inhibiting further virus replication. In addition, some chemokines orchestrate the recruitment of activated leukocytes to foci of infection to aid viral clearance. Viruses, in turn, have evolved various defences against chemokines. These range from the production of proteins that inhibit biological activity of the host chemokine to the hijacking of the chemokine system, whereby certain viruses utilize chemokine receptors for their entry. The latter viral defence can itself be blocked by chemokines. Altogether, these findings illustrate the central role of chemokines in many different phases of the immune response, particularly those aspects involving antiviral defence, a variety and versatility that was not fully appreciated even a few years ago.

Molecular determinants for CC-chemokine recognition by a poxvirus CC-chemokine inhibitor

“…Given that chemokines are so crucial to the host immune response, it is not surprising that viruses have evolved several strategies to manipulate or interfere with chemokine function (23)(24)(25). Poxviruses express a family of secreted proteins collectively known as the T1͞35kDa CC-chemokine-binding proteins (CBPs) (26).…”

Perturbation of chemokine networks by gene deletion alters the reinforcing actions of ethanol

“…Some studies showed that chemokine receptors play crucial role in human immunodeficiency virus (HIV) infection [71]. Overall, the chemokines are important components of the endogenous host defense system [54,57].…”

Subversion of the chemokine world by microbial pathogens

“…Poxvirus vCkBP-I is able to bind a wide range of chemokines through binding the conserved glycosaminoglycan (GAG) binding domain. (10) By binding the chemokines in such a manner, it prevents them from binding the extracellular matrix, and therefore prevents the formation of a stable chemokine gradient (16,30) . Poxvirus vCkBP-I is also able to function in the first manner by direct neutralisation.…”

“…This vCk is able to act as a receptor antagonist for many CC and CXC receptors. (16) As such it is able to potently inhibit chemotaxis of neutrophils, macrophages and lymphocytes. This property may account for the conspicuous absence of inflammatory cells in MCV lesions, and the delayed or absent inflammatory response.…”

“…This property may account for the conspicuous absence of inflammatory cells in MCV lesions, and the delayed or absent inflammatory response. (16,18) However, no viral mechanism is completely non-discriminating, as MC148R is not able to antagonise CCR10 or CXCR6. (18) The other example of a broad-based chemokine neutralisation, poxvirus vCkBP-II, is able to neutralise a wide variety of chemokines, but has very complex binding dynamics, so that the neutralisation is dependent on the mixture of constituents.…”