Arginine insertion and loss of N-linked glycosylation site in HIV-1 envelope V3 region confer CXCR4-tropism

Tsuchiya, Kiyoto; Ode, Hirotaka; Hayashida, Tsunefusa; Kakizawa, Junko; Sato, Hironori; Oka, Shinichi; Gatanaga, Hiroyuki

doi:10.1038/srep02389

Cited by 18 publications

(25 citation statements)

References 44 publications

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“…The lower indel rates might also be attributed in part to compensatory mutations to preserve structural interactions in V3 [28]. For example, an arginine insertion at position 11 of V3 confers CXCR4 tropism tends to be accompanied by a single amino acid deletion near the C-terminal of V3 [36].…”

Section: Discussionmentioning

confidence: 99%

“…Only a small number of comparative studies have examined indel rates in the HIV-1 env gene encoding gp120 and gp41. Wood et al [40], for one, found that indels preferentially accumulate in the variable loops of gp120 compared to the remainder of this sequence, while other studies have suggested that variable loop indels correspond with HIV-1 transmission and modulate coreceptor switching [9, 36].…”

Section: Introductionmentioning

confidence: 99%

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Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

Palmer

Poon

2018

Preprint

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1The transmission and pathogenesis of human immunodeficiency virus type 1 (HIV-1) is dispropor-2 tionately influenced by evolution in the five variable regions of the virus surface envelope glyco-3 protein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change 4 in these regions. However, the influx of indels relative to nucleotide substitutions has not yet been 5 quantified through a comparative analysis of HIV-1 sequence data. Here we develop and report 6 results from a phylogenetic method to estimate indel rates for the gp120 variable regions across 7 five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M. We pro-8 cessed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences 9 for phylogenetic analysis. In brief, our method employs maximum likelihood to reconstruct phy-10 logenies scaled in time and fits a Poisson model to the observed distribution of indels between 11 closely related pairs of sequences in the tree (cherries). The rate estimates ranged from 3.0 × 10 −5 12 to 1.5 × 10 −3 indels/nt/year and varied significantly among variable regions and subtypes. Indel 13 rates were significantly lower in the region encoding variable loop V3, and also lower for HIV-1 14 subtype B relative to other subtypes. We also found that variable loops V1, V2 and V4 tended 15 to accumulate significantly longer indels. Further, we observed that the nucleotide composition 16 of indel sequences was significantly distinct from that of the flanking sequence in HIV-1 gp120. 17Indels affected potential N-linked glycosylation sites substantially more often in V1 and V2 than 18 expected by chance, which is consistent with positive selection on glycosylation patterns within 19 these regions of gp120. These results represent the first comprehensive measures of indel rates in 20 HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for 21 further research in the molecular evolution of HIV-1. 22

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

Palmer

Poon

2018

Preprint

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“…HIV-1 Env-mediated Cell-Cell Fusion Assay-The HIV-1 Env-mediated cell-cell fusion assay was performed as described previously (25,26) with minor modifications. To prepare the effector cells, the envelope expression vector (1 g of plasmid of pCXN/Env JRFL , pCXN/Env NL4-3 , or pVSV-G) and HIV-1 "Trans-activator of Transcription" (Tat) expression vector (1 g of plasmid of pCDNA6.2/HIV-tat) were transfected into HEK293 cells (5 ϫ 10 5 cells) using Lipofectamine 2000 (Invitrogen) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Sphingomyelin Synthase 2, but Not Sphingomyelin Synthase 1, Is Involved in HIV-1 Envelope-mediated Membrane Fusion

Hayashi

Nemoto-Sasaki

Tanikawa

et al. 2014

Journal of Biological Chemistry

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Background:The roles of SMS isoforms (SMS1 and SMS2) in membrane fusion have not yet been reported. Results: Overexpression of Sms2 in Sms-deficient cells increased membrane fusion susceptibility and F-actin polymerization in the region of membrane fusion. Conclusion: SMS2 could promote membrane fusion by regulating HIV-1 Env-triggered F-actin polymerization. Significance: Our findings provide new insights into the role of SMS2 in membrane fusion.

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“…The presence of N‐linked glycosylation characteristic referred to CCR5 usage. It previously reported that loss of N‐linked glycosylation site supported for a switch in the coreceptor used and conferred to CXCR4 usage . The loss of N‐linked glycosylation site might lead to change the orientation of V3 loop and alter gp120 interaction surface for coreceptor binding and influence coreceptor usage.…”

Section: Discussionmentioning

confidence: 99%

“…It previously reported that loss of N-linked glycosylation site supported for a switch in the coreceptor used and conferred to CXCR4 usage. [33][34] and reported the concordance rates ranging from 79% to 97%. [35][36][37][38][39] Many studies determined the prevalence of HIV-1 coreceptor usage in HIV-1 infected children; they have shown that either R5 or X4 viruses can be highly observed using proviral DNA or plasma RNA.…”

Section: Prevalence Of Hiv-1 Coreceptor Usage Based On Age Year Ofmentioning

confidence: 99%

HIV‐1 coreceptor usage in perinatally infected Thai children

Samleerat

Hongjaisee

Phiayura

et al. 2017

Journal of Medical Virology

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HIV-1 coreceptor usage in children who were born to HIV-1 infected mothers in Thailand is not well characterized. Here, the prevalence of coreceptor usage and genotype among HIV-1 infected children in Thailand were observed. Proviral DNA from 284 HIV-1 infected children who received HIV-1 early infant diagnosis between 2007 and 2013 under the National AIDS Program were studied. Genotypic tropism testing was performed based on amplification of the V3 region in a triplicate nested-PCR following by DNA sequencing. HIV-1 coreceptor usage was determined using Geno2pheno with a false positive rate of 10%. Samples from 267 children were successfully amplified and coreceptor usage could be determined. Two hundred and thirty-seven (89%) children were infected with CRF01_AE, 29 (11%) were subtype B and 1 was subtype C. CCR5-using variants were found in 148 (55%) children and CXCR4-using variants were observed in 119 (45%) children. No significant differences in coreceptor usage and age, gender, signs of HIV infection, children's or maternal ARV receiving were observed. The only significant difference was found in N-linked glycosylation characteristic. This evidence showed that X4 viruses can be highly observed at an early age of children which has important clinical implications and may limit usage of CCR5 antagonist family.

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Arginine insertion and loss of N-linked glycosylation site in HIV-1 envelope V3 region confer CXCR4-tropism

Cited by 18 publications

References 44 publications

Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

Sphingomyelin Synthase 2, but Not Sphingomyelin Synthase 1, Is Involved in HIV-1 Envelope-mediated Membrane Fusion

HIV‐1 coreceptor usage in perinatally infected Thai children

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