title: Siglecs facilitate HIV-1 infection of macrophages through adhesion with viral sialic acids.
abstract: 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.
  
  
  RESULTS
  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.
  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.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Zou
authors.forename: Ashley
authors.initials: A
authors.lastname: Chastain
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ford
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trandem
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: Paul
authors.initials: P
authors.lastname: Crocker
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sun
mesh_terms: D015704:CD4 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007700:Kinetics; D037102:Lectins / Q000378:metabolism*; D008264:Macrophages / Q000821:virology*; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012794:Sialic Acids / Q000737:chemistry*
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D037102:Lectins; D011134:Polysaccharides; D011994:Recombinant Proteins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012794:Sialic Acids; C514793:gp120 protein, Human immunodeficiency virus 1