Cytokine and chemokine based control of HIV infection and replication

HIV infects and propagates into CD4(+) T lymphocytes and macrophages, altho ugh many other cell types play an important role in virus spreading and pat hogenesis. In addition to regulatory viral proteins, the cytokine network h as early been implicated as a major controller of the plastic capacity of H IV to spread productively or rather remain silently integrated in the chrom osomes of infected cells. The recent discovery of CCR5 and CXCR4 as essenti al entry co-receptors together with CD4 has highlighted a novel and potenti ally important step in the pharmacological hunt for more effective antivira l agents. In addition to regulate HIV expression and replication, several c ytokines have demonstrated the capacity of up- or down-modulating chemokine receptors including CCRS and CXCR4 with the consequence of influencing the susceptibility of T cells and macrophages to HIV infection. Pharmacologica l agents such as pertussis toxin B-oligomer have demonstrated HIV suppressi ve effects via non competitive binding of CCRS, whereas interferons or inte rleukin-16 (IL-16) can prevent post-entry steps in HIV expression. At the c linical level, several cytokines or their receptors are useful markers for monitoring disease progression and its consequence on the immune system. Cy tokine-based therapy represents a realistic complementary approach to tradi tional antiretroviral therapy potentially capable of restoring important ad aptive or innate immune functions ultimately curtailing HIV spreading and i ts consequences on the immune system, as exemplified by the experimental cl inical use of IL-2.