title: Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells.
abstract: Cell-associated HIV-1 infection has been proposed to play a pivotal role in the spread of HIV-1 infection. Granulocytes are a category of white blood cells, comprising mainly basophils, neutrophils, and eosinophils, and participate in various inflammatory reactions and defense against pathogens. Here, we investigated the role of human blood granulocytes in the dissemination of HIV-1. These cells were found to express a variety of HIV-1 attachment factors (HAFs). Basophils expressed HAFs dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM3)-grabbing nonintegrin (DC-SIGN), DC immunoreceptor (DCIR), heparan sulfate proteoglycan (HSPG), and α4β7 integrin and mediated the most efficient capture of HIV-1 on the cell surface. Neutrophils were found to express DCIR and demonstrated limited efficiency of viral capture. Eosinophils expressed α4β7 integrin but exhibited little or no virus-binding capacity. Intriguingly, following direct contact with CD4+ T cells, viruses harbored on the surface of basophils were transferred to T cells. The contact between basophils and CD4+ T cells and formation of infectious synapses appeared necessary for efficient HIV-1 spread. In HIV-1-infected individuals, the frequency of basophils remained fairly stable over the course of disease, regardless of CD4+ T depletion or the emergence of AIDS-associated opportunistic infections. Collectively, our results provide novel insights into the roles of granulocytes, particularly basophils, in HIV-1 dissemination. Thus, strategies designed to prevent basophil-mediated viral capture and transfer may be developed into a new form of therapy.
  
  
  OBJECTIVE
  Cell-associated HIV-1 infection has been proposed to play a pivotal role in the spread of HIV-1 infection. Here, we demonstrated that human blood-circulating granulocytes, particularly basophils, can capture HIV-1 and mediate viral trans-infection of CD4+ T cells. The expression of a variety of HIV-1 attachment factors, such as the C-type lectins, etc., facilitates viral capture and transfer. Intriguingly, the frequency of basophils in patients with different levels of CD4+ T counts remains fairly stable during the course of disease. Our results provide novel insights into the roles of granulocytes, particularly basophils, in HIV-1 dissemination. We suggest that strategies designed to prevent basophil-mediated viral capture and transfer may be a new direction for the development of anti-HIV therapy.
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Jiang
authors.affiliation: Department of Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao-Tong University, Shanghai, China.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Guo
authors.affiliation: Department of Infectious Diseases, The Third People's Hospital of Kunming, Kunming, Yunnan, China.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Jin
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Yu-Ye
authors.initials: YY
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China jh_wang@sibs.ac.cn.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D001491:Basophils / Q000378:metabolism / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus