A role for carbohydrates in immune evasion in AIDS

Reitter, Julie N.; Means, Robert E.; Desrosiers, Ronald C.

doi:10.1038/nm0698-679

Cited by 533 publications

(490 citation statements)

References 26 publications

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“…Additionally, with simian immunodeficiency virus it has been shown that de-glycosylation events within the V1 region of the envelope result in a virus with increased antibody neutralization potential (61). With HIV-1, the N-linked glycosylation pattern has also been shown to have a varied effect on the induction of neutralizing antibodies (44,(62)(63)(64)(65)(66)(67).…”

Section: Figmentioning

confidence: 99%

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

Pollakis

Kang

Kliphuis

et al. 2001

Journal of Biological Chemistry

206

221

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The variable V1V2 and V3 regions of the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein (gp120) can influence viral coreceptor usage. To substantiate this we generated isogenic HIV-1 molecularly cloned viruses that were composed of the HxB2 envelope backbone containing the V1V2 and V3 regions from viruses isolated from a patient progressing to disease. We show that the V3 amino acid charge per se had little influence on altering the virus coreceptor phenotype. The V1V2 region and its N-linked glycosylation degree were shown to confer CXCR4 usage and provide the virus with rapid replication kinetics. Loss of an Nlinked glycosylation site within the V3 region had a major influence on the virus switching from the R5 to X4 phenotype in a V3 charge-dependent manner. The loss of this V3 N-linked glycosylation site was also linked with the broadening of the coreceptor repertoire to incorporate CCR3. By comparing the amino acid sequences of primary HIV-1 isolates, we identified a strong association between high V3 charge and the loss of this V3 N-linked glycosylation site. These results demonstrate that the N-linked glycosylation pattern of the HIV-1 envelope can strongly influence viral coreceptor utilization and the R5 to X4 switch.

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Section: Figmentioning

confidence: 99%

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

Pollakis

Kang

Kliphuis

et al. 2001

Journal of Biological Chemistry

206

221

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“…For instance, interaction and fusion of the human immunodeficiency virus (HIV) with its target host cells is mediated by its envelope protein, gp160, which has over 50% of its mass comprising of glycans [7][8][9][10]. The high population and diverse range of glycans on this protein acts as a shield for the virus against the immune system; the glycans also mask epitopes that impact HIV disease progression [8,[11][12][13][14][15][16][17]. Consequently, conducting glycoproteomics studies on this target, defining the structures and locations of glycans in the HIV envelope protein, is important in understanding how variation in glycosylation affects the functions of this protein, and the studies may also provide valuable information that can be useful in identifying new vaccine candidates.…”

mentioning

confidence: 99%

Comparison of HPLC/ESI-FTICR MS versus MALDI-TOF/TOF MS for glycopeptide analysis of a highly glycosylated HIV envelope glycoprotein

Irungu

Zhang

et al. 2008

J. Am. Soc. Mass Spectrom.

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Defining the structures and locations of the glycans attached on secreted proteins and virus envelope proteins is important in understanding how glycosylation affects their biological properties. Glycopeptide mass spectrometry (MS)-based analysis is a very powerful, emerging approach to characterize glycoproteins, in which glycosylation sites and the corresponding glycan structures are elucidated in a single MS experiment. However, to date there is not a consensus regarding which mass spectrometric platform provides the best glycosylation coverage information. Herein, we employ two of the most widely used MS approaches, online high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ ESI-MS) and offline HPLC followed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), to determine which of the two approaches provides the best glycosylation coverage information of a complex glycoprotein, the group M consensus HIV-1 envelope, CON-S gp140⌬CFI, which has 31 potential glycosylation sites. Our results highlight differences in the informational content obtained between the two methods such as the overall number of glycosylation sites detected, the numbers of N-linked glycans present at each site, and the type of confirmatory information obtained about the glycopeptide using MS/MS experiments. The two approaches are quite complementary, both in their coverage of glycopeptides and in the information they provide in MS/MS experiments. The information in this study contributes to the field of mass spectrometry by demonstrating the strengths and limitations of two widely used MS platforms in glycoprotein analysis. (J

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“…However, viral attenuation in vivo correlated inversely with the degree of the SIV-specific antibody response and protection from the subsequent viral challenge (14). Attenuation was also achieved by deleting N-linked glycosylation sites in gp120 envelope protein (15,16), suggesting a more efficient eradication of deglycosylated viruses by antibody-and T cell-mediated immune response. Nevertheless, reversion of glycosylation site mutants was observed (15), indicating that viral replication still occurred despite the efficient immune control of deglycosylated SIV.…”

mentioning

confidence: 99%

“…Attenuation was also achieved by deleting N-linked glycosylation sites in gp120 envelope protein (15,16), suggesting a more efficient eradication of deglycosylated viruses by antibody-and T cell-mediated immune response. Nevertheless, reversion of glycosylation site mutants was observed (15), indicating that viral replication still occurred despite the efficient immune control of deglycosylated SIV. Here, we describe a gain-offunction strategy to generate a highly attenuated SIV strain endowed with a transcriptional repressor for studies in primate models.…”

mentioning

confidence: 99%

High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-κB

Quinto

Puca

Greenhouse

et al. 2004

Journal of Biological Chemistry

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NF-B/I B proteins play a major role in the transcriptional regulation of human immunodeficiency virus, type-1 (HIV-1). In the case of simian immunodeficiency virus (SIV) the cellular factors required for the viral transcriptional activation and replication in vivo remain undefined. Here, we demonstrate that the p50/p65 NF-B transcription factors enhanced the Tat-mediated transcriptional activation of SIVmac239. In addition, I B-␣S32/36A, a proteolysis-resistant inhibitor of NF-B, strongly inhibited the Tat-mediated transactivation of SIVmac239. Based on this evidence, we have generated a self-regulatory virus by endowing the genome of SIVmac239 with I B-␣S32/36A; the resulting virus, SIVI B-␣S32/36A, was nef-deleted and expressed the NF-B inhibitor. We show that SIVI B-␣S32/36A was highly and stably attenuated both in cell cultures and in vivo in rhesus macaque as compared with a nef-deleted control virus. Moreover, the high attenuation was associated with a robust immune response as measured by SIVspecific antibody production, tetramer, and intracellular IFN-␥ staining of SIV gag-specific T cells. These results underscore the crucial role of NF-B/I B proteins in the regulation of SIV replication both in cell cultures and in monkeys. Thus, inhibitors of NF-B could efficiently counteract the SIV/HIV replication in vivo and may assist in developing novel approaches for AIDS vaccine and therapy.

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A role for carbohydrates in immune evasion in AIDS

Cited by 533 publications

References 26 publications

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

Comparison of HPLC/ESI-FTICR MS versus MALDI-TOF/TOF MS for glycopeptide analysis of a highly glycosylated HIV envelope glycoprotein

High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-κB

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