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14 pages, 2572 KiB

Open AccessArticle

Neutralization Sensitivity and Evolution of Virus in a Chronic HIV-1 Clade B Infected Patient with Neutralizing Activity against Membrane-Proximal External Region

by Wenqi Tang, Zhenzhen Yuan, Zheng Wang, Li Ren, Dan Li, Shuhui Wang, Yanling Hao, Jing Li, Xiuli Shen, Yuhua Ruan, Yiming Shao and Ying Liu

Pathogens 2023, 12(3), 497; https://doi.org/10.3390/pathogens12030497 - 22 Mar 2023

Cited by 1 | Viewed by 1876

Abstract

The membrane-proximal external region (MPER) is a promising HIV-1 vaccine target owing to its linear neutralizing epitopes and highly conserved amino acids. Here, we explored the neutralization sensitivity and investigated the MPER sequences in a chronic HIV-1 infected patient with neutralizing activity against the MPER. Using single-genome amplification (SGA), 50 full-length HIV-1 envelope glycoprotein (env) genes were isolated from the patient’s plasma at two time points (2006 and 2009). The neutralization sensitivity of 14 Env-pseudoviruses to autologous plasma and monoclonal antibodies (mAbs) was evaluated. Env gene sequencing revealed that the diversity of Env increased over time and four mutation positions (659D, 662K, 671S, and 677N/R) were identified in the MPER. The K677R mutation increased the IC50 values of pseudoviruses approximately twofold for 4E10 and 2F5, and E659D increased the IC50 up to ninefold for 4E10 and fourfold for 2F5. These two mutations also decreased the contact between gp41 and mAbs. Almost all mutant pseudoviruses were resistant to autologous plasma at both the earlier and concurrent time points. Mutations 659D and 677R in the MPER decreased the neutralization sensitivity of Env-pseudoviruses, providing a detailed understanding of MPER evolution which might facilitate advances in the design of HIV-1 vaccines. Full article

(This article belongs to the Section Viral Pathogens)

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15 pages, 1585 KiB

Open AccessArticle

Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B′ Infected Plasma Donor with Broadly Neutralizing Activity

by Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao and Kunxue Hong

Vaccines 2021, 9(4), 311; https://doi.org/10.3390/vaccines9040311 - 25 Mar 2021

Cited by 8 | Viewed by 2597

Abstract

We sought to analyze the evolutionary characteristics and neutralization sensitivity of viruses in a human immunodeficiency virus type 1 (HIV-1) subtype B′ infected plasma donor with broadly neutralizing activity, which may provide information for new broadly neutralizing antibodies (bNAbs) isolation and immunogen design. A total of 83 full-length envelope genes were obtained by single-genome amplification (SGA) from the patient’s plasma at three consecutive time points (2005, 2006, and 2008) spanning four years. In addition, 28 Env-pseudotyped viruses were constructed and their neutralization sensitivity to autologous plasma and several representative bNAbs were measured. Phylogenetic analysis showed that these env sequences formed two evolutionary clusters (Cluster I and II). Cluster I viruses vanished in 2006 and then appeared as recombinants two years later. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs, including 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. We confirmed that HIV-1 continued to evolve even in the presence of bNAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure. Full article

(This article belongs to the Special Issue Next-Generation HIV Antiretroviral Therapy and Vaccine Candidates)

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20 pages, 1347 KiB

Open AccessArticle

Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection

by Sodsai Tovanabutra, Rujipas Sirijatuphat, Phuc T. Pham, Lydia Bonar, Elizabeth A. Harbolick, Meera Bose, Hongshuo Song, David Chang, Celina Oropeza, Anne Marie O’Sullivan, Joyce Balinang, Eugene Kroon, Donn J. Colby, Carlo Sacdalan, Joanna Hellmuth, Phillip Chan, Peeriya Prueksakaew, Suteeraporn Pinyakorn, Linda L. Jagodzinski, Duanghathai Sutthichom, Suwanna Pattamaswin, Mark de Souza, Robert A. Gramzinski, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich, Victor Valcour, Gustavo H. Kijak, Eric Sanders-Buell, Serena Spudich, The MHRP Viral Sequencing Core and the RV254/SEARCH 010 Study Team Show full author list Hide full author list

Cells 2019, 8(8), 902; https://doi.org/10.3390/cells8080902 - 15 Aug 2019

Cited by 19 | Viewed by 4516

Abstract

HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in pol and env using next-generation sequencing in paired plasma and cerebrospinal fluid (CSF) from 18 individuals. Different proportions of mostly minor variants were found in six of the eight multiple T/F-infected individuals, indicating enrichment of some variants in CSF that may lead to significant compartmentalization in the later stages of infection. This study provides evidence for the first time that HIV-1 compartmentalization in the CNS can occur within days of HIV-1 exposure in multiple T/F infections. Further understanding of factors that determine enrichment of T/F variants in the CNS, as well as potential long-term implications of these findings for persistence of HIV-1 reservoirs and neurological impairment in HIV, is needed. Full article

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12 pages, 1547 KiB

Open AccessArticle

Characterization of EIAV env Quasispecies during Long-Term Passage In Vitro: Gradual Loss of Pathogenicity

by Cong Liu, Xue-Feng Wang, Yan Wang, Jie Chen, Zhaohua Zhong, Yuezhi Lin and Xiaojun Wang

Viruses 2019, 11(4), 380; https://doi.org/10.3390/v11040380 - 24 Apr 2019

Cited by 6 | Viewed by 3780

Abstract

As the only widely used live lentiviral vaccine, the equine infectious anima virus (EIAV) attenuated vaccine was developed by in vitro passaging of a virulent strain for 121 generations. In our previous study, we observed that the attenuated vaccine was gradually selected under increased environmental pressure at the population level (termed a quasispecies). To further elucidate the potential correlation between viral quasispecies evolution and pathogenesis, a systematic study was performed by sequencing env using several methods. Some key mutations were identified within Env, and we observed that increased percentages of these mutations were accompanied by an increased passage number and attenuated virulence. Phylogenetic analysis revealed that env mutations related to the loss of virulence might have occurred evolutionarily. Among these mutations, deletion of amino acid 236 in the V4 region of Env resulted in the loss of one N-glycosylation site that was crucial for virulence. Notably, the 236-deleted sequence represented a “vaccine-specific” mutation that was also found in wild EIAV_LN40 strains based on single genome amplification (SGA) analysis. Therefore, our results suggest that the EIAV attenuated vaccine may originate from a branch of quasispecies of EIAV_LN40. Generally, the presented results may increase our understanding of the attenuation mechanism of the EIAV vaccine and provide more information about the evolution of other lentiviruses. Full article

(This article belongs to the Special Issue Nonprimate Lentivirus)

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18 pages, 5310 KiB

Open AccessArticle

Humoral Response to the HIV-1 Envelope V2 Region in a Thai Early Acute Infection Cohort

by Hung V. Trinh, Neelakshi Gohain, Peter T. Pham, Christopher Hamlin, Hongshuo Song, Eric Sanders-Buell, Meera Bose, Leigh A. Eller, Sodsai Tovanabutra, Nelson L. Michael, Merlin L. Robb, M. Gordon Joyce and Mangala Rao

Cells 2019, 8(4), 365; https://doi.org/10.3390/cells8040365 - 19 Apr 2019

Cited by 8 | Viewed by 4858 | Correction

Abstract

Reduced risk of HIV-1 infection correlated with antibody responses to the envelope variable 1 and 2 regions in the RV144 vaccine trial. To understand the relationship between antibody responses, V2 sequence, and structure, plasma samples (n = 16) from an early acute HIV-1 infection cohort from Thailand infected with CRF01_AE strain were analyzed for binding to V2 peptides by surface plasmon resonance. Five participants with a range of V2 binding responses at week 24 post-infection were further analyzed against a set of four overlapping V2 peptides that were designed based on envelope single-genome amplification. Antibody responses that were relatively consistent over the four segments of the V2 region or a focused response to the C-strand (residues 165–186) of the V2 region were observed. Viral escape in the V2 region resulted in significantly reduced antibody binding. Structural modeling indicated that the C-strand and the sites of viral variation were highly accessible in the open conformation of the HIV-1 Env trimer. V2 residues, 165–186 are preferentially targeted during acute infection. Residues 169–184 were also preferentially targeted by the protective immune response in the RV144 trial, thus emphasizing the importance of these residues for vaccine design. Full article

(This article belongs to the Special Issue HIV and Host Interaction)

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24 pages, 2916 KiB

Open AccessArticle

Development of a Versatile, Near Full Genome Amplification and Sequencing Approach for a Broad Variety of HIV-1 Group M Variants

by Andrew N. Banin, Michael Tuen, Jude S. Bimela, Marcel Tongo, Paul Zappile, Alireza Khodadadi-Jamayran, Aubin J. Nanfack, Josephine Meli, Xiaohong Wang, Dora Mbanya, Jeanne Ngogang, Adriana Heguy, Phillipe N. Nyambi, Charles Fokunang and Ralf Duerr

Viruses 2019, 11(4), 317; https://doi.org/10.3390/v11040317 - 1 Apr 2019

Cited by 8 | Viewed by 5091

Abstract

Near full genome sequencing (NFGS) of HIV-1 is required to assess the genetic composition of HIV-1 strains comprehensively. Population-wide, it enables a determination of the heterogeneity of HIV-1 and the emergence of novel/recombinant strains, while for each individual it constitutes a diagnostic instrument to assist targeted therapeutic measures against viral components. There is still a lack of robust and adaptable techniques for efficient NFGS from miscellaneous HIV-1 subtypes. Using rational primer design, a broad primer set was developed for the amplification and sequencing of diverse HIV-1 group M variants from plasma. Using pure subtypes as well as diverse, unique recombinant forms (URF), variable amplicon approaches were developed for NFGS comprising all functional genes. Twenty-three different genomes composed of subtypes A (A1), B, F (F2), G, CRF01_AE, CRF02_AG, and CRF22_01A1 were successfully determined. The NFGS approach was robust irrespective of viral loads (≥306 copies/mL) and amplification method. Third-generation sequencing (TGS), single genome amplification (SGA), cloning, and bulk sequencing yielded similar outcomes concerning subtype composition and recombinant breakpoint patterns. The introduction of a simple and versatile near full genome amplification, sequencing, and cloning method enables broad application in phylogenetic studies of diverse HIV-1 subtypes and can contribute to personalized HIV therapy and diagnosis. Full article

(This article belongs to the Section Animal Viruses)

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