The sense behind retroviral anti-sense transcription

Manghera, Mamneet; Magnusson, Alycia; Douville, Renée N.

doi:10.1186/s12985-016-0667-3

Cited by 13 publications

(9 citation statements)

References 92 publications

(124 reference statements)

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“…These transcripts were found in the Jurkat lymphocyte, and CD4+ T cells infected with HIV. As described above, we found antisense transcripts in these cells that were previously described (171)(172)(173)(174)(175)(176)(177)(178)(179)(180)(181), but we reported for a first time higher expression of antisense RNA in Jurkat LKO, Jurkat IBD -/-and CD4+ T BI-D treated cells compared with Jurkat WT and DMSO control cells. Our findings indicate that HIV antisense RNA is not stable and decreased significantly after 24 hpi.…”

Section: Discussion and Future Directionssupporting

confidence: 81%

“…Subsequent studies showed the HIV-1 antisense gene might give rise to several transcripts of different lengths (169,170). A number of studies have assessed the ratio of sense vs. antisense transcription from the HIV-1 proviral genome (171)(172)(173)(174)(175)(176)(177)(178)(179)(180)(181), suggesting that antisense transcripts are 100-2,500 times and 1,000 times (170,174) less abundant than sense transcripts in lymphoid and myeloid cells infected in vitro respectively (170,174). However, studies in peripheral blood mononuclear cells of early-stage asymptomatic patients assessed antisense transcription showed that it represents as low as 1.3% and as high as 94% (mean 33%) of total HIV-1 proviral transcription ( 169).…”

Section: Introductionmentioning

confidence: 99%

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Labeling HIV-1 nucleic acids during infection and effect of MOV10 in HBV replication

Chavez¹,

Nieves²

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Technical limitations in simultaneous microscopic visualization of RNA, DNA, and proteins of HIV have curtailed progress in this field. To address this need we have developed a microscopy approach, multiplex immunofluorescent cell-based detection of DNA, RNA and Protein (MICDDRP), which is based on branched DNA in situ hybridization technology. MICDDRP enables simultaneous single-cell visualization of HIV spliced and unspliced RNA, cytoplasmic and nuclear DNA, and Gag. We use MICDDRP to visualize incoming capsid cores containing RNA and/or nascent DNA and follow reverse transcription kinetics. We have also reported transcriptional "bursts" of nascent RNA from integrated proviral DNA. The major barrier towards a cure is the ability of the virus to remain dormant in long-lived cells known as the latent HIV reservoirs; however, the mechanisms that regulate latency are poorly understood. HIV-1 integration is directed to regions of the genome by the chromatin binding protein lens epitheliumderived growth factor (LEDGF/p75, referred to here as LEDGF). In the absence of LEDGF, HIV-1 infection is markedly less efficient. We report for the first time that knocking out LEDGF results in upregulation of antisense HIV-1 RNA transcription. Antisense HIV-1 transcripts are abundant in a higher proportion of cells when the Integrase-LEDGF interaction is lost, whether by knocking out LEDGF or by pharmacological inhibition. We also demonstrate that intriguingly, antisense RNA is rapidly lost from infected cells. Using a dual reporter virus to investigate the association between HIV-1 antisense RNA and latency, we have determined that antisense RNA has low expression in â€œlatentlyâ€ infected cells. Hepatitis B virus infection is a major health problem, there are more than 350 million people living with chronic HBV. Immune system can clear infection during the acute phase in immune-competent patients. A better understanding of the immune response against HBV infection may lead to new insights a find a cure. RNA helicases contribute to the immune response and some also have antiviral effects. MOV10 is a helicase RNA protein that has detrimental effect in HIV infection and HCV replication under MOV10 depletion or overexpression. Considering that HBV replication rely on reverse transcription to form DNA from pre-genomic RNA, we study the effect of MOV10 in HBV replication. Our data suggest that while MOV10 overexpression leads to HBV reduction, suppression of MOV10 enhances HBV replication.

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Section: Discussion and Future Directionssupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Labeling HIV-1 nucleic acids during infection and effect of MOV10 in HBV replication

Chavez¹,

Nieves²

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“…The three conditions tested at D1 resulted in 0.32% to 0.36% of the reads being negative sense compared to 0.27% at D0, a very small but highly significant difference ( P < 0.0001 by chi-square test) (6). This type of comparative analysis is not relevant for the chronic infection of cells by SMRV, a retrovirus for which transcription uses a DNA provirus as the matrix and leads mainly to positive- but also to negative-sense RNAs (9).…”

Section: Resultsmentioning

confidence: 99%

Adventitious Virus Detection in Cells by High-Throughput Sequencing of Newly Synthesized RNAs: Unambiguous Differentiation of Cell Infection from Carryover of Viral Nucleic Acids

Cheval

Muth

Gonzalez

et al. 2019

mSphere

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The use of high-throughput sequencing (HTS) to identify viruses in biologicals differs from current molecular approaches, since its use enables an unbiased approach to detection without the need to design specific primers to preamplify target sequences. Its broad range of detection and analytical sensitivity make it an important tool to ensure that biologicals are free from adventitious viruses. Similar to other molecular methods, however, identification of viral sequences in cells by HTS does not prove viral infection, since this could reflect carryover of inert viral sequences from reagents or other sources or the presence of transcriptionally inactive cellular sequences. Due to the broad range of detection associated with HTS, the above can potentially be perceived as a drawback for the testing of pharmaceutical biological products using this method. In order to avoid the identification of inert viral sequences, we present a methodology based on metabolic RNA labeling and sequencing, which enables the specific identification of newly synthesized viral RNAs in infected cells, resulting in the ability to unambiguously distinguish active infection by DNA or RNA viruses from inert nucleic acids. In the present study, we report the ability to differentiate Vero cells acutely infected by a single-stranded positive-sense RNA virus (tick-borne encephalitis virus) from cells which have been in contact with nonreplicating virus particles. Additionally, we also found a laboratory contamination by the squirrel monkey retrovirus of our Vero cell line, which was derived from an Old World (African green) monkey, a type of contamination which until now has been identified only in cells derived from primates from the New World. IMPORTANCE The use of high-throughput sequencing (HTS) to identify viral contamination of biological products is extremely sensitive and provides a broad range of detection. Nevertheless, viral sequences identified can also be inert. Examples include contamination resulting from reagents or the presence of inactivated viruses in animal-derived components of the cell culture medium. We therefore developed a method that relies on the sequencing of newly synthesized RNAs, an unequivocal sign of the presence of a transcriptionally active virus. This improvement in the specificity of viral testing increases the acceptability of HTS as a standard test for cells used in manufacturing biologicals and in biotherapies.

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“…All these results suggest that antisense transcription might be a rule rather than an exception in retroviruses. In this context, the study of the role exerted by antisense transcripts and potential/proven ASPs in other retroviruses, as well as in endogenous retroviruses, could be of particular interest to enhance our understanding of the impact of these retroviruses on human biology and on numerous pathologies ( Manghera et al, 2017 ). However, antisense transcription is not limited to retroviruses and has also been described in numerous other viruses, such as herpesviruses (HVs).…”

Section: Functions Of Antisense Transcripts and Antisense Proteins Inmentioning

confidence: 99%

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

et al. 2021

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It was first predicted in 1988 that there may be an Open Reading Frame (ORF) on the negative strand of the Human Immunodeficiency Virus type 1 (HIV-1) genome that could encode a protein named AntiSense Protein (ASP). In spite of some controversy, reports began to emerge some years later describing the detection of HIV-1 antisense transcripts, the presence of ASP in transfected and infected cells, and the existence of an immune response targeting ASP. Recently, it was established that the asp gene is exclusively conserved within the pandemic group M of HIV-1. In this review, we summarize the latest findings on HIV-1 antisense transcripts and ASP, and we discuss their potential functions in HIV-1 infection together with the role played by antisense transcripts and ASPs in some other viruses. Finally, we suggest pathways raised by the study of antisense transcripts and ASPs that may warrant exploration in the future.

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The sense behind retroviral anti-sense transcription

Cited by 13 publications

References 92 publications

Labeling HIV-1 nucleic acids during infection and effect of MOV10 in HBV replication

Labeling HIV-1 nucleic acids during infection and effect of MOV10 in HBV replication

Adventitious Virus Detection in Cells by High-Throughput Sequencing of Newly Synthesized RNAs: Unambiguous Differentiation of Cell Infection from Carryover of Viral Nucleic Acids

Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1

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