title: Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region.
abstract: Monocytes and monocyte-derived macrophages express relatively low levels of CD4. Despite this, macrophages can be effectively infected with human immunodeficiency virus type 1. Macrophages have a critical role in human immunodeficiency virus type 1 transmission; however, the mechanism or mechanisms of virus infection are poorly understood. We report that growth factors, such as granulocyte macrophage colony-stimulating factor and macrophage colony-stimulating factor affect the phenotypic profile and permissiveness of macrophages to human immunodeficiency virus type 1. Human immunodeficiency virus type 1 infection of monocyte-derived macrophages derived from granulocyte macrophage and macrophage colony-stimulating factors was predominantly facilitated by the sialic acid-binding immunoglobulin-like lectin-1. The number of sialic acid-binding immunoglobulin-like lectin receptors on macrophage colony-stimulating factor-derived monocyte-derived macrophages was significantly greater than on granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages, and correspondingly, human immunodeficiency virus type 1 infection was greater in the macrophage colony-stimulating factor-derived monocyte-derived macrophages. Single-genome analysis and quantitative reverse transcriptase-polymerase chain reaction revealed that the differences in infectivity was not due to differences in viral fitness or in viral variants with differential infectivity but was due to reduced viral entry into the granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages. Anti-sialic acid-binding immunoglobulin-like lectin, trimeric glycoprotein 145, and scaffolded V1V2 proteins were bound to sialic acid-binding immunoglobulin-like lectin and significantly reduced human immunodeficiency virus type 1 entry and infection. Furthermore, sialic acid residues present in the V1V2 region of the envelope protein mediated human immunodeficiency virus type 1 interaction with sialic acid-binding immunoglobulin-like lectin and entry into macrophage colony-stimulating factor-derived monocyte-derived macrophages. Removal of sialic acid residues or glycans from scaffolded V1V2 protein decreased human immunodeficiency virus type 1 infectivity. These results highlight the importance of sialic acids on the V1V2 region in binding to sialic acid-binding immunoglobulin-like lectin and suggest that the unusually long surface-exposed sialic acid-binding immunoglobulin-like lectin might aid in the capture and entry of human immunodeficiency virus type 1 into monocyte-derived macrophages.
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA;
authors.forename: Ousman
authors.initials: O
authors.lastname: Jobe
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA;
authors.forename: Hung V
authors.initials: HV
authors.lastname: Trinh
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA;
authors.forename: Jiae
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC, USA.
authors.forename: Wadad
authors.initials: W
authors.lastname: Alsalmi
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Laboratory of Molecular Virology and Pathogenesis, Viral Sequencing Core, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; and.
authors.forename: Sodsai
authors.initials: S
authors.lastname: Tovanabutra
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Host Genetics Section, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; and.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Ehrenberg
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA;
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Peachman
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC, USA.
authors.forename: Guofen
authors.initials: G
authors.lastname: Gao
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, Maryland, USA; Host Genetics Section, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; and.
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Laboratory of Molecular Virology and Pathogenesis, Viral Sequencing Core, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; and.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Virology and Pathogenesis, Viral Sequencing Core, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; and.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA;
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC, USA.
authors.forename: Venigalla B
authors.initials: VB
authors.lastname: Rao
authors.affiliation: Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; mrao@hivresearch.org.
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D009000:Monocytes / Q000166:cytology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D011991:Receptors, Virus / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D036022:Capsid Proteins; D016207:Cytokines; D011991:Receptors, Virus; D063267:Sialic Acid Binding Ig-like Lectin 1; D012794:Sialic Acids; D014759:Viral Envelope Proteins; C000020:N-acetylneuraminoyllactose; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019158:N-Acetylneuraminic Acid; D007785:Lactose
keywords: GM-CSF; M-CSF; flow cytometry; qRT-PCR; surface plasmon resonance; viral entry