Dichotomous effects of C-C chemokines in HIV-1 pathogenesis.

Chemokines play a critical role in shaping innate and adaptive immunity. These molecules also participate in maintaining the immune balance in the body. Apart from their regulatory role, these mediators are involved in several inflammatory and autoimmune diseases including viral infection such as HIV-1/AIDS. Chemokine co-receptor CCR5 and CXCR4 and their ligands significantly contribute to HIV-1 disease progression. C-C chemokines such CCL3, CCL4 and CCL5 have been shown to possess antiviral effects by binding to HIV-1 co-receptors. CCL2, a member of the C-C chemokine family, displays a different feature instead. It is a potential enhancer rather than inhibitor of viral replication, a property exhibited by most of the C-C chemokine members. In addition, the role of CCL2 is well established in forming a Th2 type of response by directing differentiation of Th0 cells towards Th2 type, a unique feature of HIV-1 disease. We propose a hypothesis in which the chemotactic nature of CCL2 drives recruitment of target cells to the site of infection as one of the mechanisms operating in vivo that favours viral replication and eventually a high viral load in infected individuals.