Regulation of human endogenous retroviruses of the W family by type III interferon λ2 and HIV in astrocytes

Astrocytes play a key role in important neurological diseases such as multiple sclerosis (MS) and neuroAIDS. The multiple sclerosis-associated retrovirus (MSRV) is an active member of the W family of human endogenous retroviruses (HERV), able to produce extracellular particles; another HERV-W element is ERVWE1, producing only an env protein, named syncytin-1, that can be found intracellularly and on the plasma-membrane, but not extracellularly. MSRVenv and syncytin-1 proteins have pro-inflammatory properties that might be pathogenic, as observed in vitro and in animal models: they may cause neuroinflammation, neurodegeneration, alterations of the immune system and stress responses; both have been suggested as co-factors triggering the immunopathogenesis of MS.λ2 has been shown to favour the replication of exogenous retroviruses, such as HIV, we designed studies to detect possible effects of IFNλ2 on the above HERV-W retroelements in U87 MG astrocytes, by using real time RT-PCR assays that can selectively identify either MSRVenv or syncytin-1 transcripts.. Treatment of astrocytes with IFNλ2 was found to enhance the expression of both MSRVenv and syncytin-1, dose-dependently. If cells are infected by HIV, the expression of both elements is modified. Surprisingly, HIV caused opposite effects on the two HERV-W retroelements, since MSRVenv transcription was up-regulated, whilst that of syncytin-1 was down-regulated. Cell pre-treatment with IFNλ2 did not alter the effects of subsequent HIV infection on MSRVenv and syncytin-1. behaves as a pro-inflammatory cytokine, that can facilitate the expression of both exogenous and endogenous human retroviruses. Since Type III IFN. This cell line has the IL-28R receptor, and is sensitive to IFNλ2. It is totally unknown the role played by Type III IFN in neuropathologies like neuro-AIDS and MS, but it could be hypothesized that IFNλ