Eight percent of human DNA consists of retroelements, remnants of ancestral infections by exogenous retroviruses. The two members of the HERV-W family are MSRV (Multiple Sclerosis Associated Retrovirus) and ERVWE1 (able to produce only the Syncytin-1 env protein). MSRV and Syncytin-1 proteins have neuro-pathogenic and immune-pathogenic properties, as demonstrated in vitro and in vivo. We evaluated the expression of transcripts using specific primers that can selectively identify either MSRV-env or Syncytin-1, and the level of proteins using Western blotting assays. To verify wheter MSRV and Syncytin-1 are activated by HIV-Tat, peripheral blood mononuclear cells (PBMC), monocyte-macrophages and astrocytes were either exposed to HIV-Tat and/or other treatments. The expression of transcripts and proteins of interest was evaluated by real-time RT-PCR and western blotting assays, respectively. The results indicate that the basal expression of both elements varies with monocyte differentiation into macrophages, in which it is highly increased, as well as the response to Tat. Interestingly, while MSRV is always upregulated by Tat, Syncytin-1 is downregulated in monocytes and upregulated in macrophages deriving from the same monocytes. The opposite regulation by Tat of MSRVenv and Syncytin-1 occurs also in U87MG astroglioma cells, while in primary human fetal astrocytes (PHFA) Tat upregulates both elements. In these cells the earliest effect of Tat is the induction of TNFα. If PHFA cells are incubated with an anti-TNFα antibody, before the exposure to Tat, the blockade of endogenous TNFα abolishes Tat stimulation of MSRVenv and Syncytin-1 expression. Within CNS, Tat-induced TNFα could induce high levels of the HERV-Ws, in macrophages and astrocytes, also without HIV replication. The indirect mechanism by which Tat activates the HERV-Ws through induction of TNFα could add a new piece to the puzzle of CNS pathogenesis, i.e. the HERV-Wenv contribute to the HIV-related neurodegeneration.

The expression of HERV-W/MSRV and Syncytin-1 endogenous retroviruses is regulated by cell differentiation and by exposure to HIV-Tat and TNF alpha / Uleri, Elena; Caocci, Maurizio; Piu, C; Serra, Caterina; Dolei, Antonina. - (2014). (Intervento presentato al convegno 2nd Italian Experience in Biomedical Research: young minds at work tenutosi a Desenzano del Garda nel 24-25 ottobre 2014).

The expression of HERV-W/MSRV and Syncytin-1 endogenous retroviruses is regulated by cell differentiation and by exposure to HIV-Tat and TNF alpha

ULERI, Elena;CAOCCI, Maurizio;SERRA, Caterina;DOLEI, Antonina
2014-01-01

Abstract

Eight percent of human DNA consists of retroelements, remnants of ancestral infections by exogenous retroviruses. The two members of the HERV-W family are MSRV (Multiple Sclerosis Associated Retrovirus) and ERVWE1 (able to produce only the Syncytin-1 env protein). MSRV and Syncytin-1 proteins have neuro-pathogenic and immune-pathogenic properties, as demonstrated in vitro and in vivo. We evaluated the expression of transcripts using specific primers that can selectively identify either MSRV-env or Syncytin-1, and the level of proteins using Western blotting assays. To verify wheter MSRV and Syncytin-1 are activated by HIV-Tat, peripheral blood mononuclear cells (PBMC), monocyte-macrophages and astrocytes were either exposed to HIV-Tat and/or other treatments. The expression of transcripts and proteins of interest was evaluated by real-time RT-PCR and western blotting assays, respectively. The results indicate that the basal expression of both elements varies with monocyte differentiation into macrophages, in which it is highly increased, as well as the response to Tat. Interestingly, while MSRV is always upregulated by Tat, Syncytin-1 is downregulated in monocytes and upregulated in macrophages deriving from the same monocytes. The opposite regulation by Tat of MSRVenv and Syncytin-1 occurs also in U87MG astroglioma cells, while in primary human fetal astrocytes (PHFA) Tat upregulates both elements. In these cells the earliest effect of Tat is the induction of TNFα. If PHFA cells are incubated with an anti-TNFα antibody, before the exposure to Tat, the blockade of endogenous TNFα abolishes Tat stimulation of MSRVenv and Syncytin-1 expression. Within CNS, Tat-induced TNFα could induce high levels of the HERV-Ws, in macrophages and astrocytes, also without HIV replication. The indirect mechanism by which Tat activates the HERV-Ws through induction of TNFα could add a new piece to the puzzle of CNS pathogenesis, i.e. the HERV-Wenv contribute to the HIV-related neurodegeneration.
2014
The expression of HERV-W/MSRV and Syncytin-1 endogenous retroviruses is regulated by cell differentiation and by exposure to HIV-Tat and TNF alpha / Uleri, Elena; Caocci, Maurizio; Piu, C; Serra, Caterina; Dolei, Antonina. - (2014). (Intervento presentato al convegno 2nd Italian Experience in Biomedical Research: young minds at work tenutosi a Desenzano del Garda nel 24-25 ottobre 2014).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/135504
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