IL-13 ACTS ON MACROPHAGES TO BLOCK THE COMPLETION OF REVERSE TRANSCRIPTION, INHIBIT VIRUS PRODUCTION, AND REDUCE VIRUS INFECTIVITY

An understanding of the immune suppression of HIV-1 replication in mac rophages continues to be a major goal of AIDS research due to the cent ral role this cell type has in AIDS pathogenesis, We have previously d iscussed the potential clinical benefits of the anti-inflammatory cyto kine interleukin-13 (IL-13), which, unlike IL-P or IL-10, has limited effects on T cell functions. In this report we extend our observations on the effects of IL-13 on HIV-1 replication in monocyte-derived macr ophages (MDM) and show redundancy with IL-4, IL-13 or IL-4 have simila r effects on HIV-1 replication in MDM when added at different times af ter infection, with the ability to decrease infectious virus release w hen added for up to 7 days after infection. Removal of IL-13 from MDM revealed a reduction of infection by 16- to 81-fold based on the absen ce of viral re-emergence from lower multiplicity of infection (m.o.i.) , The reduction of HIV-1 infectivity in MDM caused by IL-13 was furthe r characterized by studies on the formation of viral DNA over a range of m.o.i. IL-13 increased the formation of LTR DNA at the lowest m.o.i . of 0.007 while concurrently inhibiting the formation of gag DNA, a l ater reverse transcription product, at the highest m.o.i. tested, 0.62 , Overall, our data indicate that IL-13 can act on macrophages before and after HIV-1 infection by blocking the completion of reverse transc ription, decreasing virus production, and reducing the infectivity of the progeny virions.