Oligosaccharide profiles of HIV-2 external envelope glycoprotein: dependence on host cells and virus isolates

Liedtke, Steffen; Adamski, Michalina; Geyer, Rudolf; Pfützner, A; Rübsamen‐Waigmann, Helga; Geyer, Hildegard

doi:10.1093/glycob/4.4.477

Cited by 36 publications

(33 citation statements)

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“…Changes in gp120 and gp41 glycosylation patterns can strongly alter the infectivity of different strains of HIV (10)(11)(12). Several studies show that desialylation of viral particles via neuraminidase digestion enhanced the HIV/SIV infectivity (8,13,15,16,21), in general agreement with the findings in this report.…”

Section: Cd4supporting

confidence: 91%

“…Support for this idea comes from data revealing that the glycosylation patterns of the heavily glycosylated, mannose-rich gp120 (4,24) differ in a host cell-specific fashion (5,(10)(11)(12). We also find that several genes whose products degrade glycans are increased in macrophages.…”

Section: Cd4mentioning

confidence: 65%

“…The discovery that mannosidase treatment increases the infectivity of virions derived from T cells differs from pre- vious reports (8,15). However, the cellular origin of a virion is crucial to examination of glycosylation-mediated effects on infectivity due to differential exposure to a variety of different glycosylation related pathways and enzymes during virion production (10,11,23), and unlike in previous studies, the virus in this report was generated in primary macrophages and T cells.…”

Section: Cd4mentioning

confidence: 70%

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Macrophage-Derived Simian Immunodeficiency Virus Exhibits Enhanced Infectivity by Comparison with T-Cell-Derived Virus

Gaskill

Zandonatti

Gilmartin

et al. 2008

J Virol

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Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infect and productively replicate in macrophages and T lymphocytes. Here, we show that SIV virions derived from macrophages have higher levels of infectivity than those derived from T cells. The lower infectivity of T-cell-derived viruses is influenced by the quantity or type of mannose residues on the virion. Our results demonstrate that the cellular origin of a virus is a major factor in viral infectivity. Cell-type-specific factors in viral infectivity, and organ-specific or disease stage-specific differences in cellular derivation of virions, can be critical in the pathogenesis of HIV and AIDS. CD4ϩ T cells and macrophages are the major targets and sources of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). In view of the essential but highly distinct roles these cell types play in the pathogenesis of HIV (7,9,14,22), understanding how viral production in each of these cell types affects the subsequent activity of virions is important for understanding the development of disease. To determine if different factors to which virions are exposed during their generation can influence their infectivity, we generated SIV stocks from both macrophages and T cells.Two molecular clones of SIV, SIVmac316 (17) and SIVmac129 (6), were used to generate viral stocks from both macrophages and T cells. These SIV stocks (herein referred to as matching viral stocks) were derived from infection of primary rhesus monocytederived macrophages (MDM) or primary rhesus T cells. Primary MDM were derived from freshly isolated rhesus peripheral blood mononuclear cells by immunomagnetic CD11b selection and differentiated by adherence for 6 days in the presence of macrophage colony-stimulating factor (10 ng/ml). The remaining peripheral blood mononuclear cells were then subjected to CD8 immunomagnetic depletion to yield CD4 ϩ enriched cells for the primary T-cell cultures and then stimulated with phytohemagglutinin (5 g/ml) and interleukin 2 (10 ng/ml) for 3 days. Following stimulation, T cells were cultured in the presence of interleukin 2 alone for 3 additional days.Both MDM and T cells were inoculated with SIV after 6 days in culture, and cell-free supernatants from each cell type were collected daily for 8 days after SIV inoculation and stored at Ϫ80°C. Stocks were then pooled and either aliquoted and frozen or purified by ultracentrifugation over a 20% sucrose cushion to eliminate contaminating cell-derived factors such as cytokines and then aliquoted and stored at Ϫ80°C. Stocks from macrophages and T cells were collected, stored, and processed simultaneously to avoid preparation related differences in infectivity. Viral stocks were generated from a total of 12 different rhesus donors; only macrophage and T-cell stocks derived from cells isolated from a single donor at the same time were used for comparison. SIV stocks were quantified by both enzyme-linked immunosorbent assay (ELISA) for p27 Gag (Beckman-Coulter) and branched-DNA assa...

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Section: Cd4supporting

confidence: 91%

Section: Cd4mentioning

confidence: 65%

Section: Cd4mentioning

confidence: 70%

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Macrophage-Derived Simian Immunodeficiency Virus Exhibits Enhanced Infectivity by Comparison with T-Cell-Derived Virus

Gaskill

Zandonatti

Gilmartin

et al. 2008

J Virol

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“…We confirmed earlier studies that showed that Env from HIV produced in macrophages contains N-linked carbohydrate structures that are more complex than those found on virus produced in peripheral blood mononuclear cells (PBMCs) (33,34,55). This differential glycosylation of HIV Env affected interactions with DC-SIGN(R) in that HIV derived from T-cell lines or PBMCs was bound and transmitted well by these lectins, whereas HIV derived from macrophages was bound and transmitted poorly.…”

supporting

confidence: 90%

“…HIV grown in T-cell lines, PBMCs and MDMs differs in N-linked glycosylation of Env (33,34,55) with gp120 from virus grown in MDMs containing N-acetyllactosamine repeats on complex chains, resulting in a more heterogeneous pattern of glycosylation compared to gp120 from virus grown in PBMCs (33,34,55). We confirmed that gp120 from HIV and SIV grown from T-cell lines and PBMCs was more homogeneous, migrated more quickly in SDS-PAGE, and was more sensitive to Endo H digestion than when produced in MDMs, findings consistent with a greater number of high-mannose carbohydrates (Fig.…”

Section: Vol 77 2003 Dc-sign(r) Interactions With Viral Env Glycoprmentioning

confidence: 99%

Differential N-Linked Glycosylation of Human Immunodeficiency Virus and Ebola Virus Envelope Glycoproteins Modulates Interactions with DC-SIGN and DC-SIGNR

Lin

Simmons²,

Pöhlmann³

et al. 2003

J Virol

245

220

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The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)] bind and transmit human immunodeficiency virus (HIV) and simian immunodeficiency virus to T cells via the viral envelope glycoprotein (Env).Other viruses containing heavily glycosylated glycoproteins (GPs) fail to interact with DC-SIGN(R), suggesting some degree of specificity in this interaction. We show here that DC-SIGN(R) selectively interact with HIV Env and Ebola virus GPs containing more high-mannose than complex carbohydrate structures. Modulation of N-glycans on Env or GP through production of viruses in different primary cells or in the presence of the mannosidase I inhibitor deoxymannojirimycin dramatically affected DC-SIGN(R) infectivity enhancement. Further, murine leukemia virus, which typically does not interact efficiently with DC-SIGN(R), could do so when produced in the presence of deoxymannojirimycin. We predict that other viruses containing GPs with a large proportion of high-mannose N-glycans will efficiently interact with DC-SIGN(R), whereas those with solely complex N-glycans will not. Thus, the virus-producing cell type is an important factor in dictating both N-glycan status and virus interactions with DC-SIGN(R), which may impact virus tropism and transmissibility in vivo.

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Glycobiology of Viruses

Geyer¹,

Geyer²,

Ernst

et al. 2000

Carbohydrates in Chemistry and Biology

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Oligosaccharide profiles of HIV-2 external envelope glycoprotein: dependence on host cells and virus isolates

Cited by 36 publications

References 0 publications

Macrophage-Derived Simian Immunodeficiency Virus Exhibits Enhanced Infectivity by Comparison with T-Cell-Derived Virus

Macrophage-Derived Simian Immunodeficiency Virus Exhibits Enhanced Infectivity by Comparison with T-Cell-Derived Virus

Differential N-Linked Glycosylation of Human Immunodeficiency Virus and Ebola Virus Envelope Glycoproteins Modulates Interactions with DC-SIGN and DC-SIGNR

Glycobiology of Viruses

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