title: IL-13 acts on macrophages to block the completion of reverse transcription, inhibit virus production, and reduce virus infectivity.
abstract: An understanding of the immune suppression of HIV-1 replication in macrophages continues to be a major goal of AIDS research due to the central role this cell type has in AIDS pathogenesis. We have previously discussed the potential clinical benefits of the anti-inflammatory cytokine interleukin-13 (IL-13), which, unlike IL-4 or IL-10, had limited effects on T cell functions. In this report are extend our observations on the effects of IL-13 on HIV-1 replication in monocyte-derived macrophages (MDM) and show redundancy with IL-4, IL-13 or IL-4 have similar effects on HIV-1 replication in MDM when added at different times after infection, with the ability to decrease infection virus release when 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 absence 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 further 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 later 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 transcription, decreasing virus production, and reducing the infectivity of the progeny virions.
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Montaner
authors.forename: R T
authors.initials: RT
authors.lastname: Bailer
authors.forename: S
authors.initials: S
authors.lastname: Gordon
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D015750:Genes, gag; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D009000:Monocytes / Q000166:cytology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D004279:DNA, Viral; D018793:Interleukin-13; D015847:Interleukin-4; D054303:HIV Reverse Transcriptase