The HIV-1 clade C promoter is particularly well adapted to replication in the gut in primary infection

Centlivre, Mireille; Sommer, Peter; Michel, M.-L.; Fang, Raphaël Ho Tsong; Gofflo, Sandrine; Valladeau, Jenny; Schmitt, Nathalie; Wain‐Hobson, Simon; Sala, Monica

doi:10.1097/01.aids.0000216365.38572.2f

Cited by 11 publications

(5 citation statements)

References 56 publications

(96 reference statements)

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“…Each HIV-1 subtype has a specific LTR promoter configuration and even minor sequence changes in TFBSs or their arrangement can strongly influence transcriptional activity, thereby affecting viral replication and latency properties (Crotti et al , 2007; Koken et al , 1992; Montano et al , 1997; Naghavi et al , 1999; Roof et al , 2002). In a previous study, we constructed a set of isogenic viruses with subtype-specific promoter elements to investigate these functions (Centlivre et al , 2005, 2006; De Baar et al , 2000; Jeeninga et al , 2000; van der Sluis et al , 2011; van Opijnen et al , 2004a). Activation of a latent HIV-1 provirus in HIV-1-infected T-cell lines was triggered by TNFα, which activates the transcription factor NF-ĸB.…”

Section: Introductionmentioning

confidence: 99%

Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes

Sluis

Derking

Breidel

et al. 2014

Journal of General Virology

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HIV-1 transcription depends on cellular transcription factors that bind to sequences in the longterminal repeat (LTR) promoter. Each HIV-1 subtype has a specific LTR promoter configuration, and minor sequence changes in transcription factor binding sites (TFBSs) or their arrangement can influence transcriptional activity, virus replication and latency properties. Previously, we investigated the proviral latency properties of different HIV-1 subtypes in the SupT1 T cell line. Here, subtype-specific latency and replication properties were studied in primary PHA-activated T lymphocytes. No major differences in latency and replication capacity were measured among the HIV-1 subtypes. Subtype B and AE LTRs were studied in more detail with regard to a putative AP-1 binding site using luciferase reporter constructs. c-Jun, a member of the AP-1 transcription factor family, can activate both subtype B and AE LTRs, but the latter showed a stronger response, reflecting a closer match with the consensus AP-1 binding site. c-Jun overexpression enhanced Tat-mediated transcription of the viral LTR, but in the absence of Tat inhibited basal promoter activity. Thus, c-Jun can exert a positive or negative effect via the AP-1 binding site in the HIV-1 LTR promoter, depending on the presence or absence of Tat.

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Section: Introductionmentioning

confidence: 99%

Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes

Sluis

Derking

Breidel

et al. 2014

Journal of General Virology

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“…30 Non-subtype B isolates might differ in their virological characteristics from the subtype B isolates (eg, viral load, chemokine co-receptor usage, transcriptional activation in specific biological compartments). [31][32][33] However, the clinical consequences of subtype variations remain unclear.…”

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confidence: 99%

HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

2006

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The HIV-1 pandemic is a complex mix of diverse epidemics within and between countries and regions of the world, and is undoubtedly the defining public-health crisis of our time. Research has deepened our understanding of how the virus replicates, manipulates, and hides in an infected person. Although our understanding of pathogenesis and transmission dynamics has become more nuanced and prevention options have expanded, a cure or protective vaccine remains elusive. Antiretroviral treatment has transformed AIDS from an inevitably fatal condition to a chronic, manageable disease in some settings. This transformation has yet to be realised in those parts of the world that continue to bear a disproportionate burden of new HIV-1 infections and are most a % ected by increasing morbidity and mortality. This Seminar provides an update on epidemiology, pathogenesis, treatment, and prevention interventions pertinent to HIV-1. HIV pandemicAn estimated 38·6 (33·4-46·0) million people live with HIV-1 worldwide, while about 25 million have died already. 1 In 2005 alone, there were 4·1 million new HIV-1 infections and 2·8 million AIDS deaths. 1 These estimates mask the dynamic nature of this evolving epidemic in relation to temporal changes, geographic distribution, magnitude, viral diversity, and mode of transmission. Today, there is no region of the world untouched by this pandemic (figure 1). 2 Heterosexual transmission remains the dominant mode of transmission and accounts for about 85% of all HIV-1 infections. Southern Africa remains the epicentre of the pandemic and continues to have high rates of new HIV-1 infections. 3 Although overall HIV-1 prevalence remains low in the emerging epidemics in China and India, the absolute numbers, which are fast approaching those seen in southern Africa, are of concern. 1 Outside of sub-Saharan Africa, a third of all HIV-1 infections are acquired through injecting drug use, most (an estimated 8·8 million) of which are in eastern Europe and central and southeast Asia. 1 The rapid spread of HIV-1 in these regions through injecting drug use is of importance, since it is a bridge for rapid establishment of more generalised epidemics. NIH-PA Author ManuscriptA defining feature of the pandemic in the current decade is the increasing burden of HIV-1 infections in women, 4 which has additional implications for mother-to-child transmission. Women now make up about 42% of those infected worldwide; over 70% of whom live in sub-Saharan Africa. 1 Overall, a quarter of all new HIV-1 infections are in adults aged younger than 25 years. 1 HIV-1 infection rates are three to six times higher in female adolescents than in their male counterparts, 1,5-7 and this difference is attributed to sexual coupling patterns of young women with older men. Population prevalence of HIV-1 infection, concurrent sexual relationships, partner change, sexual practices, the presence of other sexually transmitted diseases, [8][9][10][11] and population mobility patterns 12-14 for economic and other reasons (eg, natu...

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“…One compensatory mechanism evolved by subtype C strains could involve higher Env levels and tolerance, favoring the long term persistence of infection, particularly via macrophages. Other compensatory mechanisms may exist elsewhere in the subtype C viral genome, such as intrinsic properties of MA or promoter-related replication advantages [129, 130] linked to AP-1 and the third NF-κB site typically found in the LTR of subtype C strains [130–132]. These findings may have consequences for vaccine design as they imply subtype-dependent differences.…”

Section: Discussionmentioning

confidence: 99%

The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission

Silva¹,

Mulinge²,

Lemaire³

et al. 2016

PLoS ONE

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The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines.

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The HIV-1 clade C promoter is particularly well adapted to replication in the gut in primary infection

Abstract: These data show that the GALT cytokine network may well favour HIV-1 clade C replication during primary infection. This could result in enhanced transmission.

Cited by 11 publications

References 56 publications

Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes

Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes

HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission

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