title: Human Mucosal Mast Cells Capture HIV-1 and Mediate Viral trans-Infection of CD4+ T Cells.
abstract: The gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4(+) T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viral trans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.
  
  
  OBJECTIVE
  In this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1 trans-infection of CD4(+) T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.
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: Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ji-Fu
authors.initials: JF
authors.lastname: Wei
authors.affiliation: Department of Surgery, Shanghai 6th People's Hospital, Shanghai Jiao-Tong University, Shanghai, China.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Surgery, Shanghai Public Health Clinical Center Affiliated with Fudan University, Shanghai, China.
authors.forename: Bao-Chi
authors.initials: BC
authors.lastname: Liu
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Clinical Experiment Center and Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China njdyb@sina.com jh_wang@sibs.ac.cn.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Ding
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China njdyb@sina.com jh_wang@sibs.ac.cn.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018562:Disease Transmission, Infectious; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology*; D008407:Mast Cells / Q000821:virology*