IL-27 Reduces Cell-Surface LDLR in Human Macrophages and Restricts VSV-G-Pseudotyped HIV infection

IL-27 reduces cell-surface LDLR in human monocyte-derived macrophages, dropping to 38.3 ± 2.6% in M-CSF-derived cells and 31.4 ± 3.2% in GM-CSF-derived cells.

• Why it matters: LDLR is a key entry receptor for VSV-G-pseudotyped viral vectors, and IL-27’s mechanism for suppressing VSV-G-HIVLuc infection in macrophages was unclear.
• What they did: Monocyte-derived macrophages differentiated with M-CSF or GM-CSF were treated with IL-27, then cell-surface LDLR (flow cytometry), LDLR transcripts (qRT-PCR), and total LDLR protein (Western blot) were measured alongside viral binding, proviral DNA, and luciferase reporter activity.
• The result: IL-27 decreased total LDLR protein to 48 ± 0.8% in M-CSF-derived macrophages, reduced viral binding to nearly 50% in GM-CSF-derived cells, lowered late reverse-transcription products to 23 ± 2.1% and 44 ± 1.5%, and reduced luciferase activity to 5.8 ± 0.4% and 5.9 ± 2.1%.