Association between gp120 envelope V1V2 and V4V5 variable loop profiles in a defined HIV-1 transmission cluster

Pollakis, Georgios; Baan, Elly; Werkhoven, Maaike B. van; Berkhout, Ben; Bakker, Margreet; Jurriaans, Suzanne; Paxton, William A.

doi:10.1097/qad.0000000000000692

Cited by 8 publications

(8 citation statements)

References 58 publications

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“…This increase in the V1-V2 length and PNGs has also been detected thorough chronic infections from early to late viral Env sampling like in our work (49). Likewise in a group of individuals infected with closely related viruses higher PNGs density has been observed in the V1-V5 region of the gp120 during chronic infection compared to those oberved during the early acute infection phase (82). In viruses from the HIV-1 subtype B, it seems that early after viral transmission to a new host a selection for viral variants with shorter variable regions and a reduced degree of PNGs occurs (83).…”

Section: Discussionmentioning

confidence: 98%

The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis

Pérez-Yanes

Pernas

Marfil

et al. 2021

Preprint

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The understanding of HIV-1 pathogenesis and clinical progression is incomplete because of the variable contribution of host, immune and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has concentrated many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller’s individuals contemporary to LTNPs or recent, named Old and Modern progressors. We analyzed the Env expression, the fusion and cell-to-cell transfer capacities as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4 and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs presenting poor viral functions and shorter sequences were associated with viremic control and the non-progressor clinical phenotype, whereas functional Envs were associated with the lack of virological control and progressor clinical phenotypes. These correlations support the central role of Env genotypic and phenotypic characteristics in the in vivo HIV-1 infection and pathogenesis.IMPORTANCEThe role of the virus in the pathogenesis of HIV-1 infection has not been investigated in isolates from individuals with different progression rates. In this work, we studied the properties of the envelope glycoprotein complex (Env) in individuals with different progression rates to elucidate its role in pathogenesis. We estimated the Env expression, the CD4 binding, the fusion and cell-to-cell viral transfer capacities that affect the infectivity of the viral Envs in recombinant viruses. The Envs from individuals which control viral replication and lack clinical progression (LTNP-ECs and vLTNPs) showed lower functional capacities than from subjects with clinical progression (Old and Modern). The functional increase of the Envs characteristics was associated with an increase in viral infectivity and in increased length of variable loops and the number of glycosylation sites of the Env (gp120/SU). These results support the concept that viral characteristics contribute to viral infection and pathogenesis.

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Section: Discussionmentioning

confidence: 98%

The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis

Pérez-Yanes

Pernas

Marfil

et al. 2021

Preprint

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“…Little is known about V4; however, V4 is thought to be critical for Env entry into specific HIV strains (Li et al, 2014), and recent studies using both sequences from the HIV database and transmission clusters have found a negative correlation between the V1V2 and V4V5 regions in terms of amino acid lengths during transmission. Notably, this correlation was lost following seroconversion (Pollakis et al, 2015), indicating that the relationship between these regions may be complex. Based on our current findings, V4 may also play an important role in transmission.…”

Section: Discussionmentioning

confidence: 99%

The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection

Dittmer

Wang

et al. 2016

Virol. Sin.

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A transmission bottleneck occurs during each human immunodeficiency virus (HIV) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus (SIV)/HIV deep transmission history and current HIV evolution within the last 15-20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, HIV may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different HIV-1 V1 mutants using different HIV-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in HIV transmission and infection.

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Section: Downloaded Frommentioning

confidence: 99%

“…However, there is still considerable debate about Env properties of TF HIV-1. A reduced glycan shield on TF HIV-1 ( 9 , 19 , 20 ) was thought to improve replicative fitness and/or host cell entry; i.e., it may be a favorable trait for transmission. However, TF clones with fewer N-linked glycan sites had no clear advantage in terms of replicative rate, receptor/coreceptor binding, or entry efficiency over HIV-1 found during chronic disease ( 11 , 12 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

Deep Gene Sequence Cluster Analyses of Multi-Virus-Infected Mucosal Tissue Reveal Enhanced Transmission of Acute HIV-1

Klein

Nankya

Nickel

et al. 2021

J Virol

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Exposure of the genital mucosa to a genetically diverse viral swarm from the donor HIV-1 can result in breakthrough and systemic infection by a single transmitted/founder (TF) virus in the recipient. The highly diverse HIV-1 envelope (Env) in this inoculating viral swarm may have critical role in transmission and subsequent immune response. Thus, chronic (Envchronic) and acute (Envacute) Env chimeric HIV-1 were tested using multi-virus competition assays in human mucosal penile and cervical tissues. Viral competition analysis revealed that Envchronic viruses resided and replicated mainly in the tissue while Envacute viruses penetrated the human tissue and established infection of CD4+ T cells more efficiently. Analysis of the replication fitness, as tested in peripheral blood mononuclear cells (PBMCs), showed similar replication fitness of Envacute and Envchronic viruses, which did not correlate with transmission fitness in penile tissue. Further, we observed that chimeric env viruses with higher replication in genital mucosal tissue (chronic Env viruses) had higher binding affinity to C-type lectins. Data presented herein suggests that the inoculating HIV-1 may be sequestered in the genital mucosal tissue (represented by chronic Env HIV-1) but that a single HIV-1 clone (e.g. acute Env HIV-1) can escape this trapped replication for systemic infection. Importance During heterosexual HIV-1 transmission, a genetic bottleneck occurs in the newly infected individual as the virus passes from the mucosa and leading to systemic infection of a single transmitted HIV-1 clone in the recipient. This bottleneck in the recipient has just been described and the mechanisms involved in this selection process have not been elucidated. However, understanding mucosal restriction is of the utmost importance to understanding dynamics of infections and to now design focused vaccines. Using our human penile and cervical mucosal tissue models for mixed HIV infections, we provide evidence that HIV-1 from acute/early as compared to chronic infection can more efficiently traverse the mucosal epithelium and transmitted to T cells, suggesting higher transmission fitness. These studies focused on the role of the HIV-1 envelope in transmission and provides strong evidence that HIV transmission may involve breaking the mucosal lectin trap.

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Association between gp120 envelope V1V2 and V4V5 variable loop profiles in a defined HIV-1 transmission cluster

Cited by 8 publications

References 58 publications

The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis

The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis

The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection

Deep Gene Sequence Cluster Analyses of Multi-Virus-Infected Mucosal Tissue Reveal Enhanced Transmission of Acute HIV-1

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