Siglecs facilitate HIV-1 infection of macrophages through adhesion with viral sialic acids

TY - JOUR

T1 - Siglecs facilitate HIV-1 infection of macrophages through adhesion with viral sialic acids

AU - Zou, Zhongcheng

AU - Chastain, Ashley

AU - Moir, Susan

AU - Ford, Jennifer

AU - Trandem, Kathryn

AU - Martinelli, Elena

AU - Cicala, Claudia

AU - Crocker, Paul

AU - Arthos, James

AU - Sun, Peter D.

PY - 2011/9/8

Y1 - 2011/9/8

N2 - Background: Human immunodeficiency virus type 1 (HIV-1) infects macrophages effectively, despite relatively low levels of cell surface-expressed CD4. Although HIV-1 infections are defined by viral tropisms according to chemokine receptor usage (R5 and X4), variations in infection are common within both R5- and X4-tropic viruses, indicating additional factors may contribute to viral tropism.Methodology and Principal Findings: Using both solution and cell surface binding experiments, we showed that R5- and X4-tropic HIV-1 gp120 proteins recognized a family of I-type lectin receptors, the Sialic acid-binding immunoglobulin-like lectins (Siglec). The recognition was through envelope-associated sialic acids that promoted viral adhesion to macrophages. The sialic acid-mediated viral-host interaction facilitated both R5-tropic pseudovirus and HIV-1(BaL) infection of macrophages. The high affinity Siglec-1 contributed the most to HIV-1 infection and the variation in Siglec-1 expression on primary macrophages from different donors was associated statistically with sialic acid-facilitated viral infection. Furthermore, envelope-associated sialoglycan variations on various strains of R5-tropic viruses also affected infection.Conclusions and Significance of the Findings: Our study showed that sialic acids on the viral envelope facilitated HIV-1 infection of macrophages through interacting with Siglec receptors, and the expression of Siglec-1 correlated with viral sialic acid-mediated host attachment. This glycan-mediated viral adhesion underscores the importance of viral sialic acids in HIV infection and pathogenesis, and suggests a novel class of antiviral compounds targeting Siglec receptors.

AB - Background: Human immunodeficiency virus type 1 (HIV-1) infects macrophages effectively, despite relatively low levels of cell surface-expressed CD4. Although HIV-1 infections are defined by viral tropisms according to chemokine receptor usage (R5 and X4), variations in infection are common within both R5- and X4-tropic viruses, indicating additional factors may contribute to viral tropism.Methodology and Principal Findings: Using both solution and cell surface binding experiments, we showed that R5- and X4-tropic HIV-1 gp120 proteins recognized a family of I-type lectin receptors, the Sialic acid-binding immunoglobulin-like lectins (Siglec). The recognition was through envelope-associated sialic acids that promoted viral adhesion to macrophages. The sialic acid-mediated viral-host interaction facilitated both R5-tropic pseudovirus and HIV-1(BaL) infection of macrophages. The high affinity Siglec-1 contributed the most to HIV-1 infection and the variation in Siglec-1 expression on primary macrophages from different donors was associated statistically with sialic acid-facilitated viral infection. Furthermore, envelope-associated sialoglycan variations on various strains of R5-tropic viruses also affected infection.Conclusions and Significance of the Findings: Our study showed that sialic acids on the viral envelope facilitated HIV-1 infection of macrophages through interacting with Siglec receptors, and the expression of Siglec-1 correlated with viral sialic acid-mediated host attachment. This glycan-mediated viral adhesion underscores the importance of viral sialic acids in HIV infection and pathogenesis, and suggests a novel class of antiviral compounds targeting Siglec receptors.

KW - Human immunodeficiency virus

KW - GP120 envelope glycoprotein

KW - Myelin-associated glycoprotein

KW - I-type lectins

KW - Influenza hemagglutinin

KW - Mannose receptor

KW - Dendritic cells

KW - B-lymphocytes

KW - Type-1

KW - Protein

U2 - 10.1371/journal.pone.0024559

DO - 10.1371/journal.pone.0024559

M3 - Article

C2 - 21931755

SN - 1932-6203

VL - 6

SP - -

JO - PLoS ONE

JF - PLoS ONE

IS - 9

M1 - e24559

ER -