Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1

Simmonds, Peter; Balfe, Peter; Ludlam, C. A.; Bishop, John O.; Brown, Andrew

doi:10.1128/jvi.64.12.5840-5850.1990

Cited by 289 publications

(105 citation statements)

References 38 publications

(54 reference statements)

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“…2A), so as to generate pseudotyped viruses. Epitope insertions were made in all five variable-loop regions on gp120, which are generally thought to be relatively surface exposed on the trimer structure, given the often-observed accumulation of mutations in these regions and elicitation of NAbs to them during infection (19,49,63,68,69). Insertions were also made in the C1 and C2 constant segments.…”

Section: Resultsmentioning

confidence: 99%

The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions

Pantophlet¹,

Wang²,

Aguilar-Sino³

et al. 2009

J Virol

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The human immunodeficiency virus type 1 (HIV-1) envelope spike is a heavily glycosylated trimeric structure in which protein surfaces conserved between different HIV-1 isolates are particularly well hidden from antibody recognition. However, even variable regions on the spike tend to be less antigenic and immunogenic than one might have anticipated for external structures. Here we show that the envelope spike of primary viruses has an ability to restrict antibody recognition of variable regions. We show that access to an artificial epitope, introduced at multiple positions across the spike, is frequently limited, even though the epitope has been inserted at surface-exposed regions on the spike. Based on the data, we posit that restricted antibody access may be the result, at least in part, of a rigidification of the epitope sequence in the context of the spike and/or a highly effective flexible arrangement of the glycan shield on primary viruses. Evolution of the HIV envelope structure to incorporate extra polypeptide sequences into nominally accessible regions with limited antibody recognition may contribute to reducing the magnitude of antibody responses during infection and allow the virus to replicate unhindered by antibody pressure for longer periods.

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Section: Resultsmentioning

confidence: 99%

The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions

Pantophlet¹,

Wang²,

Aguilar-Sino³

et al. 2009

J Virol

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“…[36][37][38][39][40][41] This low CD4 density is similar to that present on macrophages. 21 The use of single genome amplification (SGA, or template endpoint dilution PCR) to amplify and clone full-length HIV-1 env genes from patient samples without PCR recombination [43][44][45][46][47] was essential in generating biologically relavant env clones for analyses of entry phenotypes. In contrast, many early studies of HIV-1 tropism used viral isolates that were generated by culturing patient samples with PBMCs and/or cell lines.…”

Section: Course Correction: Hiv-1 Can Be R5 T Cell-tropic X4 T Cell-mentioning

confidence: 99%

The evolution of HIV-1 entry phenotypes as a guide to changing target cells

Joseph

Swanstrom

2018

Journal of Leukocyte Biology

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Summary Sentence: The R5 T cell-tropic form of HIV-1 is the most abundant form and the evolutionary precursor to X4 T cell-tropic and macrophage-tropic variants. AbstractThrough a twist of fate the most common form of HIV-1, as defined by entry phenotype, was not appreciated until recently. The entry phenotype is closely linked to the target cell and thus to virus-host interactions and pathogenesis. The most abundant form of HIV-1 uses CCR5 as the coreceptor and requires a high density of CD4 for efficient entry, defining its target cell as the CD4+ memory T cell. This is the transmitted form of the virus, the form that is found in the blood, and the form that rebounds from the latent reservoir. When CD4+/CCR5+ T cells become limiting the virus evolves to use alternative target cells to support viral replication. In the CNS, the virus can evolve to use a cell that displays only a low density of CD4, while maintaining the use of CCR5 as the coreceptor. When this evolutionary variant evolves, it must be sustaining its replication in either macrophages or microglial cells, which display only a low density of CD4 relative to that on T cells. In the blood and lymphoid system, the major switch late in disease is from T cells expressing CD4 and CCR5 to T cells expressing CD4 and CXCR4, with a change in coreceptor specificity. Thus the virus responds in two different ways to different environments when its preferred target cell becomes limiting.

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“…Significant genetic variation occurs within the human immunodeficiency virus (HIV) genome [reviewed by Leigh Brown, 19911. Many studies have shown that variation occurs in both a n inter-and intrapatient [Delassus et al, 1991[Delassus et al, , 1992Goodenow et al, 1989;Simmonds et al, 1990;Wain-Hobson, 19921 and that heterogeneity is not evenly distributed throughout the genome [Pedroza Martins et al, 1991, 19921. Thus, the hypervariable regions (Vl-V5) of the enu gene are significantly more heterogeneous than regions of the g a g gene [Leigh Brown and Monaghan, 1988;Balfe et al, 19901. The enu gene contains the principal neutralising determinant of HIV-1 [Rusche et al, 1988;Palker et al, 19881.…”

Section: Introductionmentioning

confidence: 99%

Sequence variation within the human immunodeficiency virus V3 loop at seroconversion

Ait‐Khaled

Emery

1993

Journal of Medical Virology

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Analysis of the HIV-1 V3 quasispecies present in an individual at the time of seroconversion was carried out. The polymerase chain reaction (PCR) was used to amplify proviral HIV-1 DNA extracted from peripheral blood mononuclear cells from a patient who was viraemic (p24 = 15 pg/ml) and had an equivocal HIV-1 antibody status. The PCR products were cloned and the DNA sequence determined for 15 clones. These data showed that the V3 region contained only limited sequence heterogeneity with a major variant accounting for 66% of the protein quasispecies present. The protein sequence of the principal neutralising domain on all species contained the relatively rare GPGKTL motif rather than GPGRAF. The relevance of these data for early stages of HIV infection are discussed.

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Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1

Cited by 289 publications

References 38 publications

The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions

The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions

The evolution of HIV-1 entry phenotypes as a guide to changing target cells

Sequence variation within the human immunodeficiency virus V3 loop at seroconversion

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