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Classical antiviral restriction factors promote cellular immunity by their ability to interfere with virus replication and induction of their expression by proinflammatory cytokines such as interferons. The serine incorporator proteins SERINC3 and SERINC5 potently reduce the infectivity of HIV-1 particles when overexpressed, and RNA interference or knockout approaches in T cells have indicated antiviral activity also of the endogenous proteins. Due to lack of reagents for detection of endogenous SERINC proteins, it is still unclear whether SERINC3/5 are expressed to functionally relevant levels in different primary target cells of HIV infection and how the expression levels of these innate immunity factors are regulated. In the current study, analysis of SERINC3/5 mRNA steady-state levels in primary lymphoid and monocyte-derived cells revealed selective induction of their expression upon differentiation of myeloid cells. Contrary to classical antiviral restriction factors, various antiviral α-interferon subtypes and proinflammatory interleukins had no effect on SERINC levels, which were also not dysregulated in CD4+ T cells and monocytes isolated from patients with chronic HIV-1 infection. Notably, HIV-1 particles produced by terminally differentiated monocyte-derived macrophages with high SERINC5 expression, but not by low-expressing monocytes, showed a Nef-dependent infectivity defect. Overall, these findings suggest endogenous expression of SERINC5 to antivirally active levels in macrophages. Our results classify SERINC5 as an unconventional HIV-1 restriction factor whose expression is specifically induced upon differentiation of cells towards the myeloid lineage.
This article was published in the following journal.
Name: Journal of innate immunity
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A TALE-type homeodomain protein and transcription factor that functions as a regulator of PAX6 PROTEIN expression and as an activator of PLATELET FACTOR 4 gene expression. It is essential for hematopoiesis, differentiation of MEGAKARYOCYTES, and vascular patterning. It may also have a role in the induction of myeloid leukemias.
A technique to generate restriction maps from single large DNA molecules by spreading the DNA onto a glass surface, digesting with DNA RESTRICTION ENZYMES, staining with FLUORESCENT DYES, and visualizing the DNA cleavage sites by FLUORESCENCE MICROSCOPY.
An angiogenic protein belonging to the Vascular Endothelial Growth Factor family of growth factors originally isolated and cloned from human placental cDNA library. There are four isoforms of PLGF 1-4 which result from alternative splicing. Placenta Growth Factor is secreted as a glycosylated homodimer which acts as a mitogen for endothelial cells, and its expression is markedly upregulated during hypoxia and in tissue inflammation and cancer.
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