Viral chemokine modulators

Fantuzzi L, Belardelli F, Gessani S. Monocyte/macrophage-derived CC chemokines and their modulation by HIV-1 and cytokines a complex network of interactions influencing viral replication and AIDS pathogenesis. J Leukoc Biol 2003 74(5) 719-725. 

Several opiate receptors have been identified on cells of the nervous systems of animals and humans, with mu (p), kappa (k), and gamma (y) subtypes being predominant. These classical opiate receptors are G- protein coupled 7-transmembrane molecules.27 Opiates predominantly affect immune responses directly by ligation of p, k, and y opiate receptors, as well as non-classical opiate-like receptors, on immune cells and indirectly by binding to receptors on CNS cells. Studies conducted in vitro with opiate-treated immune cells demonstrated receptor-mediated reduced phagocytosis, chemotaxis and cytokine and chemokine production. These effects are linked to modulation of host resistance to bacterial, protozoan, viral and fungal infections using animal models, cell lines and primary cells. 

An interesting question derived from these studies is why viruses utilize different strategies to modulate chemokine activity. While vCKBPs have been identified mainly in poxviruses, herpesviruses frequently encode vCKs and vCKRs. This may reflect the need to modulate different aspects of chemokine biology as a result of diverse viral replication mechanisms. 

CMV infection rarely causes overt disease in immunocompetent individuals. Even in immuncompromised patients, active viral replication does not necessarily result in end-organ disease. Factors that tilt the balance between active virus replication and CMV disease are not known. It is most likely that CMV utilizes the chemokine network to propel infected cells into an environment conducive for replication, persistence, or latency. Once there, viral modulation of chemokines could assist in avoiding immune detection of the infected cell at that site. 

The induction of apoptosis in virus-infected cells is an important defense mechanism of the host. Apoptosis of a virus-infected cell occurs either as a direct response to viral infection or on recognition of infection by the host immune system. Viruses have evolved different strategies to evade host immune responses including inhibition of antibody- and complement-mediated effects, interference with interferons, inhibition and modulation of cytokines and chemokines, blockade of antigen presentation, and also inhibition of apoptosis (Spriggs 1996 Alcami and Koszinowski 2000). 

Viral Genes that May Modulate Chemokine System Function... 

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