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Researchers at Institut Pasteur of Shanghai reveal a novel function of human granulocytes in HIV-1 infection

On May 27, Journal of Virology published an advanced research work online entitled Human blood circulating basophils capture HIV-1 and mediate viral trans-infection of CD4+ T cells from Jian-Hua WANG’s Lab, Institute Pasteur of Shanghai, Chinese Academy of Sciences. This study reveals a novel function of human granulocyte in facilitating HIV-1 trans-infection.

Granulocytes are a category of white blood cells (WBCs) characterized by the presence of lobulated nuclei and secretory granules in their cytoplasmand they are  differentiated from bone marrow hematopoietic stem cells. Blood-circulating granulocytes comprise mainly neutrophils, basophils and eosinophils. Neutrophils make up the majority (50-60%) of circulating WBCs; basophils constitute only 0.5-1%, and eosinophils less than 6%. These granulocytes are recruited to peripheral tissue under certain pathological conditions and participate in various inflammatory reactions. The potential role of granuloytes in HIV-1 infection was usually ignored due to their rare expression of HIV-1 receptor CD4 and co-receptor CXCR4., The interplay of granulocytes with HIV-1 and their contribution to HIV-1 disease progression remain elusive, although neutrophil dysfunction in HIV-1/AIDS has been reported.

Ph.D. candidate Ai-Ping JIANG and research assistant Jin-Feng JIANG purified neutrophils, basophils and eosinophils from healthy human peripheral blood and investigated their interactions with HIV-1. Three types of granulocyte were found not to support HIV-1 cis-infection but capture HIV-1 and mediate viral trans-infection of CD4+ T cells. Basophils expressed a variety of HIV-1 attachment factors, such as C-type lectin DC-SIGN and heparin sulfate proteoglycan, and thereby mediated the most efficient capture and transmission of HIV-1 for robust infection. Although DCIR was found to express on neutrophils, it had a weaker capacity for binding HIV-1gp120. The α4β7 integrin expressed on eosinophils exhibited an inactive status and limited viral capture.

By collaboration with First Affiliated Hospital of Kunming Medical University and Third People’s Hospital of Kunming, granulocyte frequencies in HIV-1 infected individuals were investigated. Blood circulating granulocytes remained fairly stable over the course of disease, regardless of CD4+ T depletion or the emergence of AIDS-associated opportunistic infections. This finding might suggest that granulocytes, particularly basophils, provide a stable cellular base for progressively capturing and thus spreading viruses, and indicate that strategies designed to prevent basophil-mediated viral capture and transfer may help to combat HIV-1 infection.

This project is funded by grants from “Hundred Talents Program” of the Chinese Academy of Sciences, the General Program from the National Natural Science Foundation of China and the Science and Technology Committee 973 Program.

 

Figure. Formation of the infectious synapses (IS) between basophil and T cell facilitates viral trans-infection. (A) Basophil-mediated HIV-1 binding, visualized by TEM; (B) IS formation between basophil and CD4+ T cell and the recruitment of HIV-1, visualized under TEM; (C) IS Formation between basophil and CD4+ T cell and the recruitment of HIV-1 and C-type lectin DC-SIGN, observed under confocal microscopy. (D) The scheme for basophil-mediated HIV-1 trans-infection of CD4+ T cells.

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