Title:The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?
Volume: 17
Issue: 1
Author(s): Daniela Angela Covino, Michela Sabbatucci and Laura Fantuzzi
Affiliation:
Keywords:
CCL2, CCR2, HIV, inflammation, pathogenesis, therapy.
Abstract: The identification of chemokine receptors as necessary co-receptors for HIV entry into target
cells represented a breakthrough in the understanding of the pathogenesis of this viral infection.
Since this initial discovery, it was unraveled that chemokines, in addition to their role in blocking viral
entry by binding to co-receptors, have other functions in HIV pathogenesis. Indeed, chemokines can
either inhibit or enhance HIV replication, and these effects may involve both entry and post-entry
events of the viral life cycle. Depending on the balance of their negative versus positive effects on HIV
replication and spreading, chemokines contribute to different outcomes of HIV pathogenesis. CCL2 is
unique among the chemokines in that mostly enhancing effects on viral replication and pathogenesis have been reported.
Either HIV infection itself or exposure to viral products can induce the expression of this chemokine and of its receptor
CCR2, and high levels of CCL2/CCR2 are indeed found in HIV-infected subjects. The CCL2/CCR2 axis is tightly linked
to the high level of immune activation and inflammation that is the hallmark of HIV infection even in patients undergoing
antiretroviral therapy. In addition, more direct effects of CCL2 on HIV replication are becoming apparent. Thus, modulation
of CCL2/CCR2-driven effects may have significant impact on HIV disease progression. In this review, we will discuss
the complex interaction between CCL2/CCR2 and HIV and the emerging therapeutic approaches based on the inhibition
of this axis.
