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Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4pos T cells and macrophages

Stefania Varchetta1, Paolo Lusso2, Kelly Hudspeth3, Joanna Mikulak3, Dalila Mele1, Stefania Paolucci4, Raffaello Cimbro2, Mauro Malnati5, Agostino Riva6, Renato Maserati7, Mario U Mondelli18 and Domenico Mavilio39*

Author Affiliations

1 Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy

2 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

3 Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

4 S. S. Virologia Molecolare, S. C. Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

5 Unit of Human Virology Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy

6 Dipartimento di Scienze Cliniche (DISC) L. Sacco Hospital-Infectious diseases and Immunopathology Section, University of Milan, Milan, Italy

7 HIV Outpatient clinic, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

8 Department of Internal Medicine, University of Pavia, Pavia, Italy

9 Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy

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Retrovirology 2013, 10:154  doi:10.1186/1742-4690-10-154

Published: 13 December 2013

Abstract

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.

Keywords:
HIV-1 infection; Siglec-7; CD4+ T cells; Macrophages; AIDS patients