Dysregulation of apoptosis and autophagy gene expression in peripheral blood mononuclear cells of efficiently treated HIV-infected patients.

Objective: We measure the transcript levels of the proapoptotic GALIG, antiapoptotic MCL1 genes and those of the autophagy genes BECN1, MAP1LC3B, ATG9a, P62/SQSTM1, GABARAP, GABARAPL1 and GABARAPL2 to define if mRNA alteration can characterize HIV-infected patients effectively treated with combined antiretroviral therapy (cART).

Design: Monocentric pilot study conducted on peripheral blood mononuclear cell (PBMC) of 40 uninfected donors and 27 HIV-positive patients effectively treated by cART for at least 8.4 years.

Opposing Mcl-1, the GALIG proapoptotic gene is upregulated as neutrophils die and underexpressed in Acute Myeloid Leukemia cells.

GALIG gene expression induces apoptosis in cultured cells through a pathway still under investigation. It is highly expressed in leukocytes but weakly detectable in bone marrow, suggesting a role in the myeloid lineage homeostasis. We show here that GALIG-induced cell death is counteracted by the overexpression of MCL-1, a pro-survival member of the Bcl2 family.

The mitogaligin protein is addressed to the nucleus via a non-classical localization signal.

Mitogaligin, a protein encoded by galig, an internal cytotoxic gene of the galectin-3 locus, is mostly a mitochondrial protein. Mitochondrial targeting is due to an already identified mitochondrial localization signal. Interaction of mitogaligin with mitochondria leads to cytochrome c cytosolic leakage and ultimately to cell death.

Inhibition of HIV replication: a powerful antiviral strategy by IFN-beta gene delivery in CD4+ cells.

In this study, we demonstrated the efficiency and feasibility of a gene therapy protocol against HIV infection using the antiviral effects of IFN-beta expression. Lentiviral vectors containing the human or the simian IFN-beta sequences under the influence of the murine moderate H2-kb promoter were constructed. To examine the capacity of IFN-beta to inhibit the replication of HIV in human CD4(+) cells, a transduction protocol permitting to efficiently transduce CD4(+) cells or PBMC (85+/-12% of CD4(+)-transduced cells) with a moderate expression of IFN-beta was developed.