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Trends in Immunology Aug 2022Despite antiretroviral therapy (ART), HIV-1 persists as proviruses integrated into the genomic DNA of CD4 T cells. The mechanisms underlying the persistence and clonal... (Review)
Review
Despite antiretroviral therapy (ART), HIV-1 persists as proviruses integrated into the genomic DNA of CD4 T cells. The mechanisms underlying the persistence and clonal expansion of these cells remain incompletely understood. Cases have been described in which proviral integration can alter host gene expression to drive cellular proliferation. Here, we review observations from other genome-integrating human viruses to propose additional putative modalities by which HIV-1 integration may alter cellular function to favor persistence, such as by altering susceptibility to cytotoxicity in virus-expressing cells. We propose that signals implicating such mechanisms may have been masked thus far by the preponderance of defective and/or nonreactivatable HIV-1 proviruses, but could be revealed by focusing on the integration sites of intact proviruses with expression potential.
Topics: Anti-Retroviral Agents; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Proviruses; Virus Integration
PubMed: 35817699
DOI: 10.1016/j.it.2022.06.001 -
MBio Jan 2019DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral... (Review)
Review
DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral expression in latency models, its correlation with HIV persistence and expression is ambiguous, particularly in persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Several factors potentially contribute to discrepancies between results in the literature, including differences in integration sites, functional proviral load, sampling bias, and stochastic PCR amplification. Recent studies into genomic features of cytosine methylation sites in mammalian genes offer potentially significant insights into this mechanism. Here, we discuss the importance of these factors in the context of the HIV.
Topics: Cytosine; DNA Methylation; DNA, Viral; Epigenesis, Genetic; Gene Expression Regulation, Viral; HIV; Proviruses; Virus Latency
PubMed: 30670613
DOI: 10.1128/mBio.02268-18 -
Viruses Jun 2016Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with human diseases, such as adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/Tropic... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with human diseases, such as adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/Tropic spastic paraparesis (HAM/TSP). As a retrovirus, its life cycle includes a step where HTLV-1 is integrated into the host genomic DNA and forms proviral DNA. In the chronic phase of the infection, HTLV‑1 is known to proliferate as a provirus via the mitotic division of the infected host cells. There are generally tens of thousands of infected clones within an infected individual. They exist not only in peripheral blood, but also in various lymphoid organs. Viral proteins encoded in HTLV-1 genome play a role in the proliferation and survival of the infected cells. As is the case with other chronic viral infections, HTLV-1 gene expression induces the activation of the host immunity against the virus. Thus, the transcription from HTLV-1 provirus needs to be controlled in order to evade the host immune surveillance. There should be a dynamic and complex regulation in vivo, where an equilibrium between viral antigen expression and host immune surveillance is achieved. The mechanisms regulating viral gene expression from the provirus are a key to understanding the persistent/latent infection with HTLV-1 and its pathogenesis. In this article, we would like to review our current understanding on this topic.
Topics: Epigenesis, Genetic; Gene Expression Regulation, Viral; Human T-lymphotropic virus 1; Humans; Proviruses; Transcription, Genetic; Virus Latency
PubMed: 27322309
DOI: 10.3390/v8060171 -
Nihon Naika Gakkai Zasshi. the Journal... Dec 2001
Review
Topics: Diabetes Mellitus, Type 1; HIV Infections; HTLV-I Infections; Humans; Proviruses
PubMed: 11917863
DOI: No ID Found -
Journal of Feline Medicine and Surgery Feb 2021
Topics: Animals; Cat Diseases; Cats; DNA, Viral; Leukemia Virus, Feline; Leukemia, Feline; Lymphoma; Prevalence; Proviruses
PubMed: 33289445
DOI: 10.1177/1098612X20979873 -
Infectious Disorders Drug Targets Dec 2006The therapeutic armamentarium for human immunodeficiency virus type 1 (HIV-1) infection continues to expand. New targets such as entry and integration have recently been... (Review)
Review
The therapeutic armamentarium for human immunodeficiency virus type 1 (HIV-1) infection continues to expand. New targets such as entry and integration have recently been successfully exploited. However, HIV-infected patients in need of treatment are currently committed to lifelong suppressive therapy. The persistence of integrated HIV DNA genomes capable of producing virus is a fundamental obstacle to the eradication or cure of HIV infection. Rational molecular or pharmacologic strategies to eliminate persistent HIV proviral genomes are an unaddressed therapeutic need. Coupled with potent antiretroviral therapy, treatments that could efficiently deplete the persistent DNA reservoir of HIV could radically alter treatment paradigms. Prior attempts to target persistent proviral infection deployed intensive antiretroviral therapy (ART) in combination with global inducers of T-cell activation. Initial trials of this approach were unsuccessful. Non-specific T-cell activation may induce high-level viral replication above a level that can be fully contained by ART, while increasing the susceptibility of uninfected cells. Selective targeting of HIV provirus via agents that induce the expression of quiescent HIV, but have limited effects on the uninfected host cell is an alternate approach to attack latent HIV. Recent studies define the role of repressive chromatin structure in maintaining HIV quiescence, and suggest that mechanisms that remodel chromatin about the HIV promoter are a possible therapeutic target. Other studies have uncovered specific factors that may act to induce or maintain latency by limiting the efficiency of HIV gene expression. Attempts to deplete latent HIV using drugs that alter chromatin structure have entered clinical study.
Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Gene Expression Regulation, Viral; HIV Infections; HIV-1; Humans; Lymphocyte Activation; Proviruses; T-Lymphocytes
PubMed: 17168802
DOI: 10.2174/187152606779025824 -
Science Advances Sep 2023The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore...
The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore sequencing, here, we captured circRNAs from HIV-1-infected T cells and identified ciTRAN, a circRNA that modulates HIV-1 transcription. We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with SRSF1, a protein known to repress HIV-1 transcription. Our results suggest that HIV-1 hijacks ciTRAN to exclude serine/arginine-rich splicing factor 1 (SRSF1) from the viral transcriptional complex, thereby promoting efficient viral transcription. In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks.
Topics: Animals; Proviruses; HIV-1; RNA, Circular; Gene Expression; Nanopores
PubMed: 37672576
DOI: 10.1126/sciadv.adh9170 -
Methods (San Diego, Calif.) Jan 2011HIV-1 latency is a barrier to overcome in the effort to fully eradicate the virus from infected individuals using highly active anti-retroviral therapy (HAART).... (Review)
Review
HIV-1 latency is a barrier to overcome in the effort to fully eradicate the virus from infected individuals using highly active anti-retroviral therapy (HAART). Therefore, the study of the mechanisms underlying the establishment and maintenance of HIV-1 latency are vital to achieving a cure. Transcriptional repression of the viral promoter is the major cause of HIV-1 latency. DNA methylation of genomic regions known as CpG islands (CpGIs) is a well-established transcriptional regulatory mechanism, and the HIV-1 provirus contains several conserved CpGIs including two that are located within the viral promoter region. The study of these CpGIs in both in vitro and in vivo models of HIV-1 latency using the technique of bisulfite-mediated methylcytosine mapping has led to their identification as factors that contribute to the maintenance of HIV-1 latency. Here, we discuss the identification of CpGIs within the HIV-1 provirus and the study of their differential methylation patterns in several HIV-1 latency models using bisulfite-mediated methylcytosine mapping.
Topics: 5-Methylcytosine; Base Sequence; Cloning, Molecular; Computer Simulation; CpG Islands; DNA Methylation; DNA, Viral; Genome, Viral; HIV Infections; HIV-1; Humans; Models, Genetic; Proviruses; Sulfites; Virus Integration; Virus Latency
PubMed: 20670606
DOI: 10.1016/j.ymeth.2010.05.009 -
Growth rate determines prokaryote-provirus network modulated by temperature and host genetic traits.Microbiome Jun 2022Prokaryote-virus interactions play key roles in driving biogeochemical cycles. However, little is known about the drivers shaping their interaction network structures,...
BACKGROUND
Prokaryote-virus interactions play key roles in driving biogeochemical cycles. However, little is known about the drivers shaping their interaction network structures, especially from the host features. Here, we compiled 7656 species-level genomes in 39 prokaryotic phyla across environments globally and explored how their interaction specialization is constrained by host life history traits, such as growth rate.
RESULTS
We first reported that host growth rate indicated by the reverse of minimal doubling time was negatively related to interaction specialization for host in host-provirus network across various ecosystems and taxonomy groups. Such a negative linear growth rate-specialization relationship (GrSR) was dependent on host optimal growth temperature (OGT), and stronger toward the two gradient ends of OGT. For instance, prokaryotic species with an OGT ≥ 40 °C showed a stronger GrSR (Pearson's r = -0.525, P < 0.001). Significant GrSRs were observed with the presences of host genes in promoting the infection cycle at stages of adsorption, establishment, and viral release, but nonsignificant with the presence of immune systems, such as restriction-modification systems and CRISPR-Cas systems. Moreover, GrSR strength was increased with the presence of temperature-dependent lytic switches, which was also confirmed by mathematical modeling.
CONCLUSIONS
Together, our results advance our understanding of the interactions between prokaryotes and proviruses and highlight the importance of host growth rate in interaction specialization during lysogenization. Video Abstract.
Topics: Ecosystem; Prokaryotic Cells; Proviruses; Temperature; Viruses
PubMed: 35701838
DOI: 10.1186/s40168-022-01288-x -
Gene Dec 2000Retroviruses are known to integrate in the host cell genome as proviruses, and therefore they are prone to cell-mediated control at the transcriptional and... (Review)
Review
Retroviruses are known to integrate in the host cell genome as proviruses, and therefore they are prone to cell-mediated control at the transcriptional and posttranscriptional levels. This plays an important role especially after retrovirus heterotransmission to foreign species, but also to differentiated cells. In addition to host cell-mediated blocks in provirus expression, also so far undefined host specificities, deciding upon the pathogenic manifestation of retrovirus heterotransmission, are in play. In this respect, we discuss especially the occurrence of wasting disease and immunodeficiency syndrome, which we established also in avian species using avian leukosis virus subgroup C (ALV-C) inoculated in mid-embryogenesis in duck or chicken embryos. The problem of provirus downregulation in foreign species or in differentiated cells has been in the recent years approached experimentally. From a series of observations it became apparent that provirus downregulation is mediated by its methylation, especially in the region of proviral enhancer-promoter located in long terminal repeats (LTR). Several strategies have been devised in order to protect the provirus from methylation using LTR modification and/or introducing in the LTR sequence motifs acting as antimethylation tags. In such a way the expression of retroviruses and vectors in foreign species, as well as in differentiated cells, has been significantly improved. The complexity of the mechanisms involved in provirus downregulation and further possibilities to modulate it are discussed.
Topics: Animals; Gene Silencing; Humans; Proviruses; Retroviridae; Species Specificity
PubMed: 11164049
DOI: 10.1016/s0378-1119(00)00481-9