Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current HIV Research
  4. Volume 22, Issue 6
  5. Article
Volume 22, Issue 6
  • ISSN: 1570-162X
  • E-ISSN: 1873-4251

Abstract

Objectives

The envelope glycoprotein (Env) on the surface of the human immunodeficiency virus (HIV-1) is a crucial protein that mediates binding to host cell receptors and subsequent membrane fusion. Env, as the sole target for neutralizing antibodies, holds unique importance in vaccine design. Therefore, analyzing the genetic characteristics of the Env region offers reference data for vaccine and drug design.

Methods

From December 2021 to December 2022, 145 newly diagnosed, HIV-1-infected individuals in Baoding City were recruited into this study. The HIV-1 env gene sequence was successfully obtained from 142 of the 145 blood specimens, and the sequences were submitted to the Quality Control Tool (http//:HIV-DB Sequence Quality Control Tool (lanl.gov)) to analyze the viral subtype. The coreceptor tropism was predicted using the Geno2pheno web tool with false-positive rate (FPR) values of 5%–15%, and the net charges of the third variable (V3) loop were calculated by Variable Region Characteristics (lanl.gov).

Results

The results showed that half of the patients were infected with the CCR5-tropic virus (50.0%, 71/142). In HIV-1 subtype CRF01_AE infection, the use of CXCR4 is expected to predominate, while in HIV-1 subtype CRF07_BC infection, CCR5 coreceptors are expected to be used predominantly. Sequence analysis of the V3 loop region revealed that subtypes CRF01_AE and CRF07_BC have similar median net charges (~3.0). Furthermore, GPGQ was found to be the major terminal tetrapeptide of the CRF07_ BC and CRF01_AE strains in this study.

Conclusion

These findings enhance our understanding of the characteristics of the HIV-1 epidemic and provide important implications for HIV-1 vaccine design and clinical treatment.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/chr/10.2174/011570162X321660241127102018
2024-12-01
2025-01-20

  • From This Site

    /content/journals/chr/10.2174/011570162X321660241127102018
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BolivarH. GeffinR. ManziG. The challenge of HIV-1 genetic diversity: discordant CD4+ T-Cell count and viral load in an untreated patient infected with a subtype F strain.J. Acquir. Immune Defic. Syndr.200952565966110.1097/QAI.0b013e3181b72539 19935211
     [Google Scholar]
  2. RobertsonD.L. AndersonJ.P. BradacJ.A. HIV-1 nomenclature proposal.Science20002885463555610.1126/science.288.5463.55d 10766634
     [Google Scholar]
  3. LiX. LiuH. LiuL. Tracing the epidemic history of HIV-1 CRF01_AE clusters using near-complete genome sequences.Sci. Rep.201771402410.1038/s41598‑017‑03820‑8
     [Google Scholar]
  4. FengY. TakebeY. WeiH. Geographic origin and evolutionary history of China’s two predominant HIV-1 circulating recombinant forms, CRF07_BC and CRF08_BC.Sci. Rep.2016611927910.1038/srep19279 26763952
     [Google Scholar]
  5. NasirA. DimitrijevicM. Romero-SeversonE. LeitnerT. Large evolutionary rate heterogeneity among and within HIV-1 subtypes and CRFs.Viruses2021139168910.3390/v13091689 34578270
     [Google Scholar]
  6. SchlubT.E. GrimmA.J. SmythR.P. Fifteen to twenty percent of HIV substitution mutations are associated with recombination.J. Virol.20148873837384910.1128/JVI.03136‑13 24453357
     [Google Scholar]
  7. Global HIV & AIDS statistics — Fact sheet.2021.2021Available from: https://www.unaids.org/en/resources/fact-sheet
  8. DumasF PreiraP SaloméL Membrane organization of virus and target cell plays a role in HIV entry.Biochimie2014107Pt A222710.1016/j.biochi.2014.08.015
     [Google Scholar]
  9. BergerE.A. DomsR.W. FenyöE.M. A new classification for HIV-1.Nature1998391666424010.1038/34571 9440686
     [Google Scholar]
  10. WilenC.B. TiltonJ.C. DomsR.W. HIV: Cell binding and entry.Cold Spring Harb. Perspect. Med.201228a00686610.1101/cshperspect.a006866 22908191
     [Google Scholar]
  11. BergerE.A. MurphyP.M. FarberJ.M. Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease.Annu. Rev. Immunol.199917165770010.1146/annurev.immunol.17.1.657 10358771
     [Google Scholar]
  12. ConnellB.J. HermansL.E. WensingA.M.J. Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection.Sci. Rep.20201011586610.1038/s41598‑020‑71699‑z 32985522
     [Google Scholar]
  13. KeeleB.F. GiorgiE.E. Salazar-GonzalezJ.F. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.Proc. Natl. Acad. Sci. USA2008105217552755710.1073/pnas.0802203105 18490657
     [Google Scholar]
  14. NaifH.M. Pathogenesis of HIV infection.Infect. Dis. Rep.2013511Suppl. 1e610.4081/idr.2013.s1.e6 24470970
     [Google Scholar]
  15. GorryP.R. AncutaP. Coreceptors and HIV-1 pathogenesis.Curr. HIV/AIDS Rep.201181455310.1007/s11904‑010‑0069‑x 21188555
     [Google Scholar]
  16. HayashidaT. TsuchiyaK. KikuchiY. OkaS. GatanagaH. Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors.PLoS One2017125e017703310.1371/journal.pone.0177033 28472121
     [Google Scholar]
  17. SavkovicB. SymondsG. MurrayJ.M. Stochastic model of in-vivo X4 emergence during HIV infection: Implications for the CCR5 inhibitor maraviroc.PLoS One201277e3875510.1371/journal.pone.0038755 22866173
     [Google Scholar]
  18. WeinbergerA.D. PerelsonA.S. Persistence and emergence of X4 virus in HIV infection.Math. Biosci. Eng.20118260562610.3934/mbe.2011.8.605 21631149
     [Google Scholar]
  19. PanR. QinY. BanasikM. Increased epitope complexity correlated with antibody affinity maturation and a novel binding mode revealed by structures of rabbit antibodies against the third variable loop (V3) of HIV-1 gp120.J. Virol.2018927e01894e1710.1128/JVI.01894‑17 29343576
     [Google Scholar]
  20. ZhuR. SangX. ZhouJ. CXCR4 recognition by L- and D-peptides containing the full-length V3 loop of HIV-1 gp120.Viruses2023155108410.3390/v15051084 37243169
     [Google Scholar]
  21. HillM.D. LorenzoE. KumarA. Changes in the human immunodeficiency virus V3 region that correspond with disease progression: A meta-analysis.Virus Res.20041061273310.1016/j.virusres.2004.05.013 15522444
     [Google Scholar]
  22. McKeatingJ.A. BalfeP. The role of the viral glycoprotein in HIV-1 persistence.Immunol. Lett.1999651-2637010.1016/S0165‑2478(98)00126‑6 10065629
     [Google Scholar]
  23. ArrildtK.T. JosephS.B. SwanstromR. The HIV-1 Env protein: A coat of many colors.Curr. HIV/AIDS Rep.201291526310.1007/s11904‑011‑0107‑3 22237899
     [Google Scholar]
  24. ZhaoC. LiH. SwartzT.H. ChenB.K. The HIV Env glycoprotein conformational states on cells and viruses.MBio2022132e01825e2110.1128/mbio.01825‑21 35323042
     [Google Scholar]
  25. LadinskyM.S. GnanapragasamP.N.P. YangZ. WestA.P. KayM.S. BjorkmanP.J. Electron tomography visualization of HIV-1 fusion with target cells using fusion inhibitors to trap the pre-hairpin intermediate.eLife20209e5841110.7554/eLife.58411 32697193
     [Google Scholar]
  26. BeitariS. WangY. LiuS.L. LiangC. HIV-1 envelope glycoprotein at the interface of host restriction and virus evasion.Viruses201911431110.3390/v11040311 30935048
     [Google Scholar]
  27. PerrinJ. BaryA. VernayA. CossonP. Role of the HIV-1 envelope transmembrane domain in intracellular sorting.BMC Cell Biol.2018191310.1186/s12860‑018‑0153‑4 29544440
     [Google Scholar]
  28. DerkingR. SandersR.W. Structure-guided envelope trimer design in HIV-1 vaccine development: A narrative review.J. Int. AIDS Soc.202124Suppl. 7e2579710.1002/jia2.25797
     [Google Scholar]
  29. PerdigueroB. HauserA. GómezC.E. Potency and durability of T and B cell immune responses after homologous and heterologous vector delivery of a trimer-stabilized, membrane-displayed HIV-1 clade ConC Env protein.Front. Immunol.202314127090810.3389/fimmu.2023.1270908 38045703
     [Google Scholar]
  30. ZhouT. XuL. DeyB. Structural definition of a conserved neutralization epitope on HIV-1 gp120.Nature2007445712973273710.1038/nature05580 17301785
     [Google Scholar]
  31. KwongP.D. DoyleM.L. CasperD.J. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites.Nature2002420691667868210.1038/nature01188 12478295
     [Google Scholar]
  32. ScanlanC.N. PantophletR. WormaldM.R. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1->2 mannose residues on the outer face of gp120.J. Virol.200276147306732110.1128/JVI.76.14.7306‑7321.2002 12072529
     [Google Scholar]
  33. LuX. ZhangJ. WangY. Large transmission clusters of HIV-1 main genotypes among HIV-1 individuals before antiretroviral therapy in the Hebei province, China.AIDS Res. Hum. Retroviruses202036542743310.1089/aid.2019.0199 31595767
     [Google Scholar]
  34. FanW. WangX. ZhangY. Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Baoding, Hebei province, China.Front. Genet.20221397539710.3389/fgene.2022.975397 36186451
     [Google Scholar]
  35. ShiP. ChenZ. MengJ. Molecular transmission networks and pre-treatment drug resistance among individuals with acute HIV-1 infection in Baoding, China.PLoS One20211612e026067010.1371/journal.pone.0260670 34855860
     [Google Scholar]
  36. ShiP. WangX. FanW. Pre-treatment drug resistance analysis of HIV-1 infected patients in Baoding City, 2019-2020.Chin J Dermatovenereol202135091012101610.13735/j.cjdv.1001‑7089.202103052
     [Google Scholar]
  37. FanW. XingY. HanL. HIV-1 genetic characteristics and pre-treatment drug resistance among newly diagnosed population in Baoding, Hebei Province.Chin. J. Microbiol. Immunol.20224202889310.3760/cma.j.cn112309‑20210814‑00272
     [Google Scholar]
  38. GeZ. FengY. ZhangH. HIV-1 CRF07_BC transmission dynamics in China: Two decades of national molecular surveillance.Emerg. Microbes Infect.20211011919193010.1080/22221751.2021.1978822 34498547
     [Google Scholar]
  39. OkudaK. BukawaH. KawamotoS. A serologic analysis and the amino acid sequence of the V3 region of human immunodeficiency virus from carriers in Bangkok.J. Infect. Dis.1994169122722810.1093/infdis/169.1.227 8277190
     [Google Scholar]
  40. ShiodaT. LevyJ.A. Cheng-MayerC. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1.Proc. Natl. Acad. Sci. USA199289209434943810.1073/pnas.89.20.9434 1409653
     [Google Scholar]
  41. IsakaY. SatoA. MikiS. Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5.Virology1999264123724310.1006/viro.1999.0006 10544150
     [Google Scholar]
  42. KoitoA. StamatatosL. Cheng-MayerC. Small amino acid sequence changes within the V2 domain can affect the function of a T-cell line-tropic human immunodeficiency virus type 1 envelope gp120.Virology1995206287888410.1006/viro.1995.1010 7856100
     [Google Scholar]
  43. IvanoffL.A. DubayJ.W. MorrisJ.F. V3 Loop region of the HIV-1 gpl20 envelope protein is essential for virus infectivity.Virology1992187242343210.1016/0042‑6822(92)90444‑T 1546447
     [Google Scholar]
  44. GuoJ.L. YanY. ZhangJ.F. Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.Epidemiol. Infect.2019147e18110.1017/S0950268819000700 31063103
     [Google Scholar]
  45. HuX. FengY. LiK. Unique profile of predominant CCR5-tropic in CRF07_BC HIV-1 infections and discovery of an unusual CXCR4-tropic strain.Front. Immunol.20221391180610.3389/fimmu.2022.911806 36211390
     [Google Scholar]
  46. IrlbeckD.M. Amrine-MadsenH. KitrinosK.M. LaBrancheC.C. DemarestJ.F. Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals.AIDS200822121425143110.1097/QAD.0b013e32830184ba 18614865
     [Google Scholar]
  47. ZhangL. MaL. WangZ. Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for coreceptor switching in CRF07_BC in China.PLoS One201493e9342610.1371/journal.pone.0093426 24676404
     [Google Scholar]
  48. SchuitemakerH. van ’t WoutA.B. LussoP. Clinical significance of HIV-1 coreceptor usage.J. Transl. Med.20119Suppl. 1S510.1186/1479‑5876‑9‑S1‑S5
     [Google Scholar]
  49. GorryP.R. ChurchillM. CroweS.M. CunninghamA.L. GabuzdaD. Pathogenesis of macrophage tropic HIV-1.Curr. HIV Res.200531536010.2174/1570162052772951 15638723
     [Google Scholar]
  50. GorryP.R. SterjovskiJ. ChurchillM. The role of viral coreceptors and enhanced macrophage tropism in human immunodeficiency virus type 1 disease progression.Sex. Health200411233410.1071/SH03006 16335478
     [Google Scholar]
  51. MaedaY. TakemuraT. ChikataT. Existence of replication-competent minor variants with different coreceptor usage in plasma from HIV-1-infected individuals.J. Virol.20209412e00193e2010.1128/JVI.00193‑20 32295903
     [Google Scholar]
  52. ZhangC. LanY. LiL. HIV-1 tropism in low-level viral load HIV-1 infections during HAART in Guangdong, China.Front. Microbiol.202314115976310.3389/fmicb.2023.1159763
     [Google Scholar]
  53. GrayL. SterjovskiJ. ChurchillM. Uncoupling coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from macrophage tropism reveals biological properties of CCR5-restricted HIV-1 isolates from patients with acquired immunodeficiency syndrome.Virology2005337238439810.1016/j.virol.2005.04.034 15916792
     [Google Scholar]
  54. CowleyS. The biology of HIV infection.Lepr. Rev.200172221222010.5935/0305‑7518.20010028 11495453
     [Google Scholar]
  55. CeresolaE.R. NozzaS. SampaoloM. Performance of commonly used genotypic assays and comparison with phenotypic assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients.J. Antimicrob. Chemother.20157051391139510.1093/jac/dku573 25608585
     [Google Scholar]
  56. ChenX. WangZ.X. PanX.M. HIV-1 tropism prediction by the XGboost and HMM methods.Sci. Rep.201991999710.1038/s41598‑019‑46420‑4 31292462
     [Google Scholar]
  57. PhuphuakratA. PhawattanakulS. PasomsubE. KiertiburanakulS. ChantratitaW. SungkanuparphS. Coreceptor tropism determined by genotypic assay in HIV -1 circulating in T hailand, where CRF01_AE predominates.HIV Med.201415526927510.1111/hiv.12108 24215399
     [Google Scholar]
  58. FerreiraJ.L.P. CoelhoL.P.O. RodriguesR. Evaluation of genotypic prediction of HIV-1 tropism using population sequencing of replicates.J. Virol. Methods2012179232532910.1016/j.jviromet.2011.11.018 22138669
     [Google Scholar]
  59. RiemenschneiderM. CashinK.Y. BudeusB. Genotypic prediction of co-receptor tropism of HIV-1 subtypes A and C.Sci. Rep.2016612488310.1038/srep24883 27126912
     [Google Scholar]
  60. RaymondS. DelobelP. RogezS. Genotypic prediction of HIV-1 CRF01-AE tropism.J. Clin. Microbiol.201351256457010.1128/JCM.02328‑12 23224099
     [Google Scholar]
  61. DelgadoE. Fernández-GarcíaA. VegaY. Evaluation of genotypic tropism prediction tests compared with in vitro co-receptor usage in HIV-1 primary isolates of diverse subtypes.J. Antimicrob. Chemother.2012671253110.1093/jac/dkr438 22010208
     [Google Scholar]
  62. RaymondS. DelobelP. MavignerM. Correlation between genotypic predictions based on V3 sequences and phenotypic determination of HIV-1 tropism.AIDS20082214F11F1610.1097/QAD.0b013e32830ebcd4 18753930
     [Google Scholar]
  63. GarridoC. RouletV. ChuecaN. Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes.J. Clin. Microbiol.200846388789110.1128/JCM.01611‑07 18199789
     [Google Scholar]
  64. GhosnJ. BayanT. MeixenbergerK. CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus.J. Antimicrob. Chemother.201772102862286810.1093/jac/dkx247 29091208
     [Google Scholar]
  65. Sierra-EnguitaR. RodriguezC. AguileraA. X4 tropic viruses are on the rise in recent HIV-1 seroconverters in Spain.AIDS201428111603160910.1097/QAD.0000000000000269 24637545
     [Google Scholar]
  66. BrummeZ.L. GoodrichJ. MayerH.B. Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals.J. Infect. Dis.2005192346647410.1086/431519 15995960
     [Google Scholar]
  67. ChalmetK. DauweK. FoquetL. Presence of CXCR4-using HIV-1 in patients with recently diagnosed infection: correlates and evidence for transmission.J. Infect. Dis.2012205217418410.1093/infdis/jir714 22147802
     [Google Scholar]
  68. LiX. XueY. ZhouL. Evidence that HIV-1 CRF01_AE is associated with low CD4+T cell count and CXCR4 co-receptor usage in recently infected young men who have sex with men (MSM) in Shanghai, China.PLoS One201492e8946210.1371/journal.pone.0089462 24586795
     [Google Scholar]
  69. ToS.W.C. ChenJ.H.K. WongK.H. ChanK.C.W. ChenZ. YamW.C. Determination of the high prevalence of Dual/Mixed- or X4-tropism among HIV type 1 CRF01_AE in Hong Kong by genotyping and phenotyping methods.AIDS Res. Hum. Retroviruses20132981123112810.1089/aid.2013.0067 23647565
     [Google Scholar]
  70. de MendozaC. RodriguezC. GarcíaF. Prevalence of X4 tropic viruses in patients recently infected with HIV-1 and lack of association with transmission of drug resistance.J. Antimicrob. Chemother.200759469870410.1093/jac/dkm012 17327295
     [Google Scholar]
  71. Smoleń-DzirbaJ RosińskaM KruszyńskiP Transmission patterns of HIV-1 non-R5 strains in Poland.Sci Rep201991497010.1038/s41598‑019‑41407‑7 30899060
     [Google Scholar]
  72. LiK. ChenH. LiJ. Distinct genetic clusters in HIV-1 CRF01_AE-infected patients induced variable degrees of CD4 + T-cell loss.MBio2024153e03349e2310.1128/mbio.03349‑23 38385695
     [Google Scholar]
  73. LiY. HanY. XieJ. CRF01_AE subtype is associated with X4 tropism and fast HIV progression in Chinese patients infected through sexual transmission.AIDS201428452153010.1097/QAD.0000000000000125 24472744
     [Google Scholar]
  74. NgK.Y. ChewK.K. KaurP. High prevalence of CXCR4 usage among treatment-naive CRF01_AE and CRF51_01B-infected HIV-1 subjects in Singapore.BMC Infect. Dis.20131319010.1186/1471‑2334‑13‑90 23421710
     [Google Scholar]
  75. GeZ. FengY. LiK. CRF01_AE and CRF01_AE Cluster 4 are associated with poor immune recovery in Chinese patients under combination antiretroviral therapy.Clin. Infect. Dis.202172101799180910.1093/cid/ciaa380 32296820
     [Google Scholar]
  76. VandekerckhoveL.P.R. WensingA.M.J. KaiserR. European guidelines on the clinical management of HIV-1 tropism testing.Lancet Infect. Dis.201111539440710.1016/S1473‑3099(10)70319‑4 21429803
     [Google Scholar]
  77. KootM. KeetI.P. VosA.H. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS.Ann. Intern. Med.1993118968168810.7326/0003‑4819‑118‑9‑199305010‑00004 8096374
     [Google Scholar]
  78. MaasJ.J.J. GangeS.J. SchuitemakerH. CoutinhoR.A. LeeuwenR. MargolickJ.B. Strong association between failure of T cell homeostasis and the syncytium-inducing phenotype among HIV-1-infected men in the Amsterdam cohort study.AIDS20001491155116110.1097/00002030‑200006160‑00012 10894279
     [Google Scholar]
/content/journals/chr/10.2174/011570162X321660241127102018
Loading
Genetic Characteristics of the Env Regions in HIV-1-Infected Subjects in Baoding City, Hebei Province, China
Current HIV Research 22, 409 (2024); https://doi.org/10.2174/011570162X321660241127102018
/content/journals/chr/10.2174/011570162X321660241127102018
/content/journals/chr/10.2174/011570162X321660241127102018
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): CCR5-tropic virus; coreceptor tropism; CRF01_AE; CRF07_BC; CXCR4; Env; HIV-1
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test