Evidence for replication of human endogenous retroviruses type-K (HERV-K) in HIV-1 positive patients

Contreras-Galindo, Rafael; Contreras-Galindo, Angie C.; Lorenzo, Eric; Yamamura, Yuichi

doi:10.1186/1742-4690-3-s1-s33

Cited by 4 publications

(3 citation statements)

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“…However, the level of HML-2 induction in HIV infection remains unclear. Several studies have found that HML-2 RNA was readily detectable in plasma of HIV-infected individuals (Contreras-Galindo et al 2006; Contreras-Galindo, Almodovar-Camacho, et al 2007; Contreras-Galindo, Lopez, et al 2007; Contreras-Galindo et al 2012; Esqueda et al 2013); however, other investigators were unable to confirm these findings (Bhardwaj et al 2014; Karamitros et al 2016). It has been suggested that contamination with genomic DNA is largely responsible for detection of HML-2 in blood, since rigorous DNA digestion with DNase I eliminated HML-2 from almost all patient samples (Esqueda et al 2013; Bhardwaj et al 2014; Karamitros et al 2016).…”

Section: Hml-2 In Pathological Conditionsmentioning

confidence: 99%

Human endogenous retrovirus-K (HML-2): a comprehensive review

García-Montojo

Doucet-O’Hare

Henderson

et al. 2018

Critical Reviews in Microbiology

161

164

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The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered “junk DNA” and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.

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Section: Hml-2 In Pathological Conditionsmentioning

confidence: 99%

Human endogenous retrovirus-K (HML-2): a comprehensive review

García-Montojo

Doucet-O’Hare

Henderson

et al. 2018

Critical Reviews in Microbiology

161

164

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“…Endogenous Prot genes may help exogenous retroviruses, such as lentiviruses, to infect the host cells. The primate lentiviruses HIV and simian immunodeficiency virus (SIV) do not express their own dUTPase, and it is believed that a host cell-endogenous retroviral enzyme (Prot) provides this activity during reverse transcription [125,126,127], in line with the recent observations that HIV-1 infection may increase the expression of HERV-K (HML-2) proviruses in vitro [128] and in vivo [129,130]. Rec and Np9 activities may interfere with normal nuclear cytoplasmic transport mechanisms [131] or even serve as inducers of organ-specific tumorogenesis [102].…”

Section: Expression Of Viral Proteinsmentioning

confidence: 89%

“…Inspection of human transcript databases (the present study) revealed four different RNAs that terminate at human-specific LTRs (elements 126,128,129,139 [ Supplementary Table 1]). Among these transcripts, three RNAs lack any ORFs, whereas one (BC092439) encodes for a 8-kDa protein of unknown function, highly similar to human protein GON4L, a transcription factor that may function in cell cycle control [144].…”

Section: Ltr Polyadenylation Signalsmentioning

confidence: 99%

Human-Specific Endogenous Retroviruses

Buzdin

2007

The Scientific World JOURNAL

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This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

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HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression

Badarinarayan

Shcherbakova

Langer

et al. 2020

Nucleic Acids Research

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Although endogenous retroviruses (ERVs) are known to harbor cis-regulatory elements, their role in modulating cellular immune responses remains poorly understood. Using an RNA-seq approach, we show that several members of the ERV9 lineage, particularly LTR12C elements, are activated upon HIV-1 infection of primary CD4+ T cells. Intriguingly, HIV-1-induced ERVs harboring transcription start sites are primarily found in the vicinity of immunity genes. For example, HIV-1 infection activates LTR12C elements upstream of the interferon-inducible genes GBP2 and GBP5 that encode for broad-spectrum antiviral factors. Reporter assays demonstrated that these LTR12C elements drive gene expression in primary CD4+ T cells. In line with this, HIV-1 infection triggered the expression of a unique GBP2 transcript variant by activating a cryptic transcription start site within LTR12C. Furthermore, stimulation with HIV-1-induced cytokines increased GBP2 and GBP5 expression in human cells, but not in macaque cells that naturally lack the GBP5 gene and the LTR12C element upstream of GBP2. Finally, our findings suggest that GBP2 and GBP5 have already been active against ancient viral pathogens as they suppress the maturation of the extinct retrovirus HERV-K (HML-2). In summary, our findings uncover how human cells can exploit remnants of once-infectious retroviruses to regulate antiviral gene expression.

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Evidence for replication of human endogenous retroviruses type-K (HERV-K) in HIV-1 positive patients

Cited by 4 publications

References 0 publications

Human endogenous retrovirus-K (HML-2): a comprehensive review

Human endogenous retrovirus-K (HML-2): a comprehensive review

Human-Specific Endogenous Retroviruses

HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression

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