HIV-1 Infection Causes a Down-Regulation of Genes Involved in Ribosome Biogenesis

Kleinman, Claudia L.; Doria, Margherita; Orecchini, Elisa; Giuliani, Erica; Galardi, Silvia; Jay, Nicolas; Michienzi, Alessandro

doi:10.1371/journal.pone.0113908

Cited by 23 publications

(21 citation statements)

References 51 publications

(68 reference statements)

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“…The cause of this downregulation of ribosomal protein transcription remains uncertain. However, similar findings have been reported for primary CD4 ϩ T cells and Jurkat T cell lines in which pre-rRNA processing was perturbed in HIV infection (41,42). Several of these ribosomal genes are in the pathway downstream of eIF2.…”

Section: Discussionsupporting

confidence: 82%

Persistent Replication of HIV, Hepatitis C Virus (HCV), and HBV Results in Distinct Gene Expression Profiles by Human NK Cells

Boeijen

Hou

Groen

et al. 2019

J Virol

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NK cells during chronic viral infection have been well studied in the past. We performed an unbiased next-generation RNA-sequencing approach to identify commonalities or differences of the effect of HIV, HCV and HBV viremia on NK cell transcriptomes. Using cell sorting, we obtained CD3-CD56+ NK cells from blood of 6 HIV, 8 HCV, and 32 HBV infected patients without treatment. After library preparation and sequencing, we used an in-house analytic pipeline to compare expression levels with matched healthy controls. In NK cells from HIV, HCV and HBV patients, transcriptome analysis identified 272, 53, and 56 differentially expressed genes, respectively (fold change >1.5, q-value 0.2). Interferon stimulated genes were induced in NK cells from HIV/HCV patients, but not during HBV infection. HIV viremia downregulated ribosome assembly genes in NK cells. In HBV, viral load and ALT variation had little effect on genes related to NK effector function. In conclusion, we compare, for the first time, NK cell transcripts of viremic HIV, HCV and HBV patients. We clearly demonstrate distinctive NK cell gene signatures in 3 different populations, suggestive for a different degree of functional alterations of the NK cell compartment as compared to healthy individuals. Three viruses exist that can result in persistently high viral loads in immune competent humans: HIV, hepatitis C and hepatitis B. In the last decades, using flow cytometry and in vitro assays on NK cells from patients with these diseases, several impairments have been established, particularly during and possibly contributing to HIV viremia. However, the background of NK cell impairments in viremic patients is not well understood. In this study we describe the NK cell transcriptome of patients with high viral loads of different etiologies. We clearly demonstrate distinctive NK cell gene signatures, with regard to ISG induction, expression of genes coding for activation markers or proteins involved in cytotoxic action, as well immunological genes. This study provides important details necessary to uncover the origin of functional and phenotypical differences between viremic patients and healthy subjects, and provides many leads that can be confirmed using future in vitro manipulation experiments.

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Section: Discussionsupporting

confidence: 82%

Persistent Replication of HIV, Hepatitis C Virus (HCV), and HBV Results in Distinct Gene Expression Profiles by Human NK Cells

Boeijen

Hou

Groen

et al. 2019

J Virol

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“…The functional subnetwork containing the ribosome component proteins did not show a statistically significant change, and with this, we can demonstrate on protein level the same findings observed by Kleinman et.al. at gene level, who could not observe statistically significant difference in case of genes having a role in ribosome biogenesis at 12 h time point [34]. Regarding the other cluster containing mainly hnRNP proteins, we could not observe a statistically significant change in network parameters among the different time points.…”

Section: Go1902580 Single-organism Cellular Localization Df Decreasecontrasting

confidence: 66%

Analysis of networks of host proteins in the early time points following HIV transduction

et al. 2019

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Background: Utilization of quantitative proteomics data on the network level is still a challenge in proteomics data analysis. Currently existing models use sophisticated, sometimes hard to implement analysis techniques. Our aim was to generate a relatively simple strategy for quantitative proteomics data analysis in order to utilize as much of the data generated in a proteomics experiment as possible. Results: In this study, we applied label-free proteomics, and generated a network model utilizing both qualitative, and quantitative data, in order to examine the early host response to Human Immunodeficiency Virus type 1 (HIV-1). A weighted network model was generated based on the amount of proteins measured by mass spectrometry, and analysis of weighted networks and functional sub-networks revealed upregulation of proteins involved in translation, transcription, and DNA condensation in the early phase of the viral life-cycle. Conclusion: A relatively simple strategy for network analysis was created and applied to examine the effect of HIV-1 on host cellular proteome. We believe that our model may prove beneficial in creating algorithms, allowing for both quantitative and qualitative studies of proteome change in various biological and pathological processes by quantitative mass spectrometry.

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“…Changes in host cell gene expression have been reported during HIV infection [ 17 – 29 ] and differences in expression have been observed associated with the stage [ 30 ] and progression [ 31 ] of disease. Multiple studies suggest that cells detect HIV infection, in part through the recognition of cytoplasmic DNA in abortive infections [ 32 – 34 ], and respond by inducing interferon-regulated, apoptotic and stress response pathways [ 18 – 22 , 25 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

Gene activity in primary T cells infected with HIV89.6: intron retention and induction of genomic repeats

2015

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Background: HIV infection has been reported to alter cellular gene activity, but published studies have commonly assayed transformed cell lines and lab-adapted HIV strains, yielding inconsistent results. Here we carried out a deep RNA-Seq analysis of primary human T cells infected with the low passage HIV isolate HIV 89.6 .Results: Seventeen percent of cellular genes showed altered activity 48 h after infection. In a meta-analysis including four other studies, our data differed from studies of HIV infection in cell lines but showed more parallels with infections of primary cells. We found a global trend toward retention of introns after infection, suggestive of a novel cellular response to infection. HIV 89.6 infection was also associated with activation of several human endogenous retroviruses (HERVs) and retrotransposons, of interest as possible novel antigens that could serve as vaccine targets. The most highly activated group of HERVs was a subset of the ERV-9. Analysis showed that activation was associated with a particular variant of ERV-9 long terminal repeats that contains an indel near the U3-R border. These data also allowed quantification of >70 splice forms of the HIV 89.6 RNA and specified the main types of chimeric HIV 89.6 -host RNAs. Comparison to over 100,000 integration site sequences from the same infected cell populations allowed quantification of authentic versus artifactual chimeric reads, showing that 5′ read-in, splicing out of HIV 89.6 from the D4 donor and 3′ read-through were the most common HIV 89.6 -host cell chimeric RNA forms. Conclusions:Analysis of RNA abundance after infection of primary T cells with the low passage HIV 89.6 isolate disclosed multiple novel features of HIV-host interactions, notably intron retention and induction of transcription of retrotransposons and endogenous retroviruses.

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HIV-1 Infection Causes a Down-Regulation of Genes Involved in Ribosome Biogenesis

Cited by 23 publications

References 51 publications

Persistent Replication of HIV, Hepatitis C Virus (HCV), and HBV Results in Distinct Gene Expression Profiles by Human NK Cells

Persistent Replication of HIV, Hepatitis C Virus (HCV), and HBV Results in Distinct Gene Expression Profiles by Human NK Cells

Analysis of networks of host proteins in the early time points following HIV transduction

Gene activity in primary T cells infected with HIV89.6: intron retention and induction of genomic repeats

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