LPS reduces HIV-1 replication in primary human macrophages partly through an endogenous production of type I interferons.
It has been proposed that the systemic immune activation state seen in HIV-1-infected patients is caused by circulating microbial products such as lipopolysaccharide (LPS). Given that macrophages play a key role in HIV-1 pathogenesis, we investigated the LPS-mediated effect on HIV-1 replication in cells of the myeloid lineage. We demonstrate that LPS promotes virus gene expression in a monocytic cell line while it diminishes virus production in primary human monocyte-derived macrophages (MDM). The incapacity of LPS to drive HIV-1 production in MDM was not due to its inability to activate the ubiquitous transcription factor NF-kappaB even in virus-infected cells. Neutralization of type I interferons (IFN) with B18R, a soluble vaccinia virus-coded type I IFN receptor, significantly but not totally diminished the antiviral activity of LPS. Therefore, inhibition of HIV-1 replication in MDM treated with microbial-derived LPS resulted from the induction of type I interferons and a yet to be defined soluble factor.
Simard
Sébastien
S
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Département de biologie médicale, Faculté de médecine, Université Laval, Québec, Canada.
Maurais
Emilie
E
Gilbert
Caroline
C
Tremblay
Michel J
MJ
D002460:Cell Line; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D016328:NF-kappa B / Q000276:immunology; D015728:Receptors, HIV / Q000276:immunology; D014162:Transfection; D014764:Viral Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D007370:Interferon Type I; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D015728:Receptors, HIV; D014764:Viral Proteins; C067853:B18R protein, Vaccinia virus; D049452:Green Fluorescent Proteins