title: Galectin-3 promotes caspase-independent cell death of HIV-1-infected macrophages.
abstract: 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 THP1 monocytes (THP1-MNs) and THP1-derived macrophages (THP1-MΦs) as in vitro cellular models. We found that THP1-MΦs were more resistant than the THP1-MNs to HIV-1 infection-induced death, and that HIV-1 infection of the THP1-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 THP1-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 SIVmac251-infected macaques compared to that of macrophages from healthy macaques. Furthermore, galectin-3-induced cell death in HIV-1-infected THP1-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 THP1-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.
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Fu
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cong
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Peng
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Zhuoying
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008251:Macaca; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000254:growth & development; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D037502:Galectin 3; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D004706:Endodeoxyribonucleases; C052391:endonuclease G
keywords: HIV-1; SIV; cell death; galectin-3; macrophages