Galectin‐3 promotes caspase‐independent cell death of HIV ‐1‐infected macrophages

HIV ‐1‐infected macrophages are a key contributor to the formation of a viral reservoir and new treatment strategies focus on eliminating this pool of virus. Galectin‐3 is a potent apoptosis‐inducing protein that regulates diverse cellular activities. In the present study, we investigated whether galectin‐3 could induce cell death in HIV ‐1‐infected macrophages using HIV ‐1‐infected THP 1 monocytes ( THP 1‐ MN s) and THP 1‐derived macrophages ( THP 1‐MΦs) as in vitro cellular models. We found that THP 1‐MΦs were more resistant than the THP 1‐ MN s to HIV ‐1 infection‐induced death, and that HIV ‐1 infection of the THP 1‐MΦs increased expression of the anti‐apoptotic proteins Mcl‐1, Bcl‐2 and Bcl‐ xL . Additionally, galectin‐3 but not FasL, tumor necrosis factor ( TNF )‐related apoptosis‐inducing ligand or TNF ‐α, could induce cell death in HIV ‐1‐infected THP 1‐MΦs. A similar result was shown for primary human monocyte‐derived macrophages. Galectin‐3‐induced cell death was also significantly increased in macrophages obtained from SIV mac251‐infected macaques compared to that of macrophages from healthy macaques. Furthermore, galectin‐3‐induced cell death in HIV ‐1‐infected THP 1‐MΦs was caspase independent. Interestingly, endonuclease G (Endo G) was increased in the nucleus and decreased in the cytoplasm of galectin‐3‐treated cells; thus, galectin‐3‐induced cell death in HIV ‐1‐infected THP 1‐MΦs is most likely related to the translocation of Endo G from the cytoplasm to the nucleus. These findings suggest that galectin‐3 may potentially aid in the eradication of HIV ‐1/ SIV ‐infected macrophages.