Retrovirology | |
Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4pos T cells and macrophages | |
Domenico Mavilio4  Mario U Mondelli9  Renato Maserati8  Agostino Riva1  Mauro Malnati7  Raffaello Cimbro5  Stefania Paolucci3  Dalila Mele6  Joanna Mikulak2  Kelly Hudspeth2  Paolo Lusso5  Stefania Varchetta6  | |
[1] Dipartimento di Scienze Cliniche (DISC) L. Sacco Hospital-Infectious diseases and Immunopathology Section, University of Milan, Milan, Italy;Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy;S. S. Virologia Molecolare, S. C. Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy;Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy;Unit of Human Virology Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy;HIV Outpatient clinic, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;Department of Internal Medicine, University of Pavia, Pavia, Italy | |
关键词: AIDS patients; Macrophages; CD4+ T cells; Siglec-7; HIV-1 infection; | |
Others : 805805 DOI : 10.1186/1742-4690-10-154 |
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received in 2013-06-26, accepted in 2013-12-10, 发布年份 2013 | |
【 摘 要 】
Background
Sialic acid-binding Ig-like lectin-7 (Siglec-7) expression is strongly reduced on natural killer (NK) cells from HIV-1 infected viremic patients. To investigate the mechanism(s) underlying this phenomenon, we hypothesized that Siglec-7 could contribute to the infection of CD4pos target cells following its interaction with HIV-1 envelope (Env) glycoprotein 120 (gp120).
Results
The ability of Siglec-7 to bind gp120 Env in a sialic acid-dependent manner facilitates the infection of both T cells and monocyte-derived macrophages (MDMs). Indeed, pre-incubation of HIV-1 with soluble Siglec-7 (sSiglec-7) increases the infection rate of CD4pos T cells, which do not constitutively express Siglec-7. Conversely, selective blockade of Siglec-7 markedly reduces the degree of HIV-1 infection in Siglec-7pos MDMs. Finally, the sSiglec-7 amount is increased in the serum of AIDS patients with high levels of HIV-1 viremia and inversely correlates with CD4pos T cell counts.
Conclusions
Our results show that Siglec-7 binds HIV-1 and contributes to enhance the susceptibility to infection of CD4pos T cells and MDMs. This phenomenon plays a role in HIV-1 pathogenesis and in disease progression, as suggested by the inverse correlation between high serum level of sSiglec-7 and the low CD4pos T cell count observed in AIDS patients in the presence of chronic viral replication.
【 授权许可】
2013 Varchetta et al.; licensee BioMed Central Ltd.
【 预 览 】
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