Rapid HIV Progression During Acute HIV-1 Subtype C Infection in a Mozambican Patient with Atypical Seroconversion

Velasco, César; Parker, Erica; Pastor, Lucía; Nhama, Abel; Macuacua, Salésio; Mandomando, Inácio; Blanco, Julià; Naniche, Denise

doi:10.4269/ajtmh.14-0554

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…Virological factors that impair the in vivo viral fitness have also been shown to contribute to this phenotype 5 . In an opposed setting, high levels of viral replication, either as a consequence of poor or inefficient immunological responses or particular viral cytopathic factors, are associated with rapid progression to AIDS 6–8 .…”

Section: Introductionmentioning

confidence: 99%

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic

Cabrera-Rodríguez

Hebmann

Marfil

et al. 2019

Sci Rep

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In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4 + T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype. Full-length Env clones isolated from individuals with Viral Load (VL) > 10,000 copies/mL classified as VNPs (n = 15) or rapid progressors (RPs, n = 17) were geno- and phenotypically analyzed by determining diversity, expression, CD4 binding/signaling, fusogenicity, infectivity and autophagy induction. Selected Env clones from VNPs and RPs (n = 32) showed similar expression, fusion and infection abilities. Env clones from both groups showed similar affinity for CD4 during cell-to-cell transmission and consistently induced similar levels of CD4 signaling, measured by α-tubulin acetylation. Moreover, we demonstrate for the first time that primary Env clones from VNP and RP induce autophagy in uninfected cells and that this feature correlated with fusogenic capacity but was unrelated to disease progression. In conclusion, our data suggest that Env clones from VNP individuals are fully functional. Therefore, the paradoxical CD4 + T cell count stability coexisting with high levels of viral replication is unrelated to Env function.

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Section: Introductionmentioning

confidence: 99%

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic

Cabrera-Rodríguez

Hebmann

Marfil

et al. 2019

Sci Rep

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“…Previous work has demonstrated that circulating virus in Mozambique is almost exclusively HIV-1 Group M subtype C ( Engelbrecht et al., 1998 ; Bellocchi et al., 2005 ; Parreira et al., 2006 ). One acute HIV case was the subject of a published case report ( Velasco et al., 2015 ) and had sequencing completed to confirm subtype C.…”

Section: Methodsmentioning

confidence: 99%

Gene dysregulation in acute HIV-1 infection – early transcriptomic analysis reveals the crucial biological functions affected

Parker

Judge

Pastor

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionTranscriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens.MethodsA hospital symptom-based screening approach was applied in a rural Mozambican setting to enrol patients with suspected acute HIV infection (Fiebig stage I-IV). Blood samples were collected from all those recruited, so that acute cases and contemporaneously recruited, uninfected controls were included. PBMC were isolated and sequenced using RNA-seq. Sample cellular composition was estimated from gene expression data. Differential gene expression analysis was completed, and correlations were determined between viral load and differential gene expression. Biological implications were examined using Cytoscape, gene set enrichment analysis, and enrichment mapping.ResultsTwenty-nine HIV infected subjects one month from presentation and 46 uninfected controls were included in this study. Subjects with acute HIV infection demonstrated profound gene dysregulation, with 6131 (almost 13% of the genome mapped in this study) significantly differentially expressed. Viral load was correlated with 1.6% of dysregulated genes, in particular, highly upregulated genes involved in key cell cycle functions, were correlated with viremia. The most profoundly upregulated biological functions related to cell cycle regulation, in particular, CDCA7 may drive aberrant cell division, promoted by overexpressed E2F family proteins. Also upregulated were DNA repair and replication, microtubule and spindle organization, and immune activation and response. The interferome of acute HIV was characterized by broad activation of interferon-stimulated genes with antiviral functions, most notably IFI27 and OTOF. BCL2 downregulation alongside upregulation of several apoptotic trigger genes and downstream effectors may contribute to cycle arrest and apoptosis. Transmembrane protein 155 (TMEM155) was consistently highly overexpressed during acute infection, with roles hitherto unknown.DiscussionOur study contributes to a better understanding of the mechanisms of early HIV-induced immune damage. These findings have the potential to lead to new earlier interventions that improve outcomes.

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Rapid HIV Progression During Acute HIV-1 Subtype C Infection in a Mozambican Patient with Atypical Seroconversion

Cited by 2 publications

References 23 publications

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic

Gene dysregulation in acute HIV-1 infection – early transcriptomic analysis reveals the crucial biological functions affected

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