• ERV9
• HDAC inhibitor
• LTR12
• cancer
• endogenous retroviruses
• innate immunity

• Endogenous Retroviruses/genetics
• Humans
• Terminal Repeat Sequences/genetics
• Gene Expression Regulation
• Epigenesis, Genetic
• Genome, Human
• Animals

• SA 2676/3-1, SFB 1506 Deutsche Forschungsgemeinschaft (DFG)
• China Scholarship Council (CSC)

• HIV-1
• HSVtk/GCV
• MT: Oligonucleotides: Therapies and Applications
• RNA trans-splicing
• gene therapy
• herpes simplex virus
• latency reversing agents
• latent reservoir
• lentiviral vector
• shock and kill

• MC_PC_13059 Medical Research Council

• AIDS
• CD4+ T cells subtypes
• HAART
• HIV infection
• resting cells
• “Kick and Kill”

• Humans
• HIV Infections/immunology
• HIV Infections/virology
• CD4-Positive T-Lymphocytes/immunology
• T-Lymphocytes, Regulatory/immunology
• HIV-1/immunology
• T-Lymphocyte Subsets/immunology
• T-Lymphocyte Subsets/metabolism

• JAK2 gene
• goat
• growth traits
• insertion/deletion
• marker-assisted selection (MAS)

• hiv-1 reservoir
• hiv-1 latency
• mechanisms of hiv-1 persistence
• clonal expansion dynamics
• single-cell rna-seq
• single-cell atac-seq
• t cell receptor sequencing
• bioinformatic analysis
• hiv-1 genome mapping
• hiv-1 cure strategies

• Humans
• HIV-1/genetics
• Virus Latency/genetics
• CD4-Positive T-Lymphocytes
• HIV Infections/genetics
• HIV Infections/drug therapy
• Multiomics
• RNA, Viral/genetics
• Epigenesis, Genetic

• R61 DA047037 NIDA NIH HHS
• R01 DA051906 NIDA NIH HHS
• UM1 AI164565 NIAID NIH HHS
• UM1 DA051410 NIDA NIH HHS
• UM1 AI164570 NIAID NIH HHS
• R01 AI145164 NIAID NIH HHS
• R33 DA047037 NIDA NIH HHS
• U01 DA053628 NIDA NIH HHS
• U54 AI170856 NIAID NIH HHS
• P50 AI150464 NIAID NIH HHS
• P01 AI169768 NIAID NIH HHS
• R01 AI174863 NIAID NIH HHS
• R01 AI141009 NIAID NIH HHS
• R37 AI147868 NIAID NIH HHS

• CFAP43
• InDel (insertion/deletion)
• body traits
• correlation analysis
• goat

• Humans
• HIV Infections
• Liver Neoplasms
• RNA-Seq
• Sequence Analysis, RNA
• Software
• Viruses

• R01 DA051906 NIDA NIH HHS
• R01 NS128523 NINDS NIH HHS
• U01 DA053628 NIDA NIH HHS
• K01 MH123896 NIMH NIH HHS
• R01 HG012572 NHGRI NIH HHS
• National Institutes of Health (US)

• CD4-Positive T-Lymphocytes
• HIV Infections
• HIV-1/genetics
• Humans
• RNA, Messenger/genetics
• Virus Latency/genetics

• National Health and Medical Research Council
• Australian Centre for HIV and Hepatitis Virology Research

• hiv
• gene-editing
• crispr/cas9
• ltr
• treg
• persistence
• insertional-mutagenesis
• integration-site

• Basic-Leucine Zipper Transcription Factors/genetics
• CRISPR-Cas Systems
• HIV Long Terminal Repeat/genetics
• HIV-1/genetics
• Humans
• Virus Integration

• R01 DA040532 NIDA NIH HHS
• R61 DA047010 NIDA NIH HHS
• R01 CA206466 NCI NIH HHS
• R33 AI122361 NIAID NIH HHS
• R01 AI134419 NIAID NIH HHS
• R21 AI122361 NIAID NIH HHS
• P30 AI027757 NIAID NIH HHS
• R01 AI125026 NIAID NIH HHS

Antiretroviral therapy (ART) suppresses HIV-1 replication but does not eradicate the virus. Persistence of HIV-1 latent reservoirs in ART-treated individuals is considered the main obstacle to achieving an HIV-1 cure. However, these HIV-1 reservoirs are not transcriptionally silent, and viral transcripts can be detected in most ART-treated individuals. HIV-1 latency is regulated at the transcriptional and at multiple post-transcriptional levels. Here, we review recent insights into the possible contribution of viral RNA processing to the persistence of HIV-1 reservoirs, and discuss the clinical implications of persistence of viral RNA species in ART-treated individuals.

• HIV-1 latency
• HIV-1 persistence
• HIV-1 reservoir
• RNA processing
• splicing

• Anti-Retroviral Agents/therapeutic use
• Disease Reservoirs/virology
• HIV Infections/drug therapy
• HIV Infections/genetics
• HIV Infections/virology
• HIV-1/genetics
• Persistent Infection/genetics
• RNA Splicing/genetics
• Virus Latency/genetics
• Virus Replication

• HIV
• Vpr
• transcriptomics
• virus-host interactions

• Apoptosis
• CD4-Positive T-Lymphocytes/virology
• Cells, Cultured
• HIV-1/genetics
• HIV-1/pathogenicity
• Host-Pathogen Interactions
• Humans
• Time Factors
• Transcriptome/genetics
• Virus Replication
• vpr Gene Products, Human Immunodeficiency Virus/genetics

• G1000196 Medical Research Council
• G0401570 Medical Research Council
• Department of Health
• 106223/Z/14/Z Wellcome Trust
• Wellcome Trust
• 103407/Z/13/Z Wellcome Trust
• R01 DA033773 NIDA NIH HHS
• MR/M019756/1 Medical Research Council
• UKRI | Medical Research Council (MRC)
• Wellcome
• HHS | National Institutes of Health (NIH)
• European Commission (EC)

Alternative splicing and the expression of intron-containing mRNAs is one hallmark of HIV gene expression. To facilitate the otherwise hampered nuclear export of non-fully processed mRNAs, HIV encodes the Rev protein, which recognizes its intronic response element and fuels the HIV RNAs into the CRM-1-dependent nuclear protein export pathway. Both alternative splicing and Rev-dependency are regulated by the primary HIV RNA sequence. Here, we show that these processes are extremely sensitive to sequence alterations in the 5’coding region of the HIV genomic RNA. Increasing the GC content by insertion of either GFP or silent mutations activates a cryptic splice donor site in gag, entirely deregulates the viral splicing pattern, and lowers infectivity. Interestingly, an adaptation of the inserted GFP sequence toward an HIV-like nucleotide bias reversed these phenotypes completely. Of note, the adaptation yielded completely different primary sequences although encoding the same amino acids. Thus, the phenotypes solely depend on the nucleotide composition of the two GFP versions. This is a strong indication of an HIV-specific mRNP code in the 5′ gag region wherein the primary RNA sequence bias creates motifs for RNA-binding proteins and controls the fate of the HIV-RNA in terms of viral gene expression and infectivity.

• HIV gene expression
• U1 snRNP
• alternative splicing
• mRNP code

• Alternative Splicing
• HEK293 Cells
• HIV Infections/virology
• HIV-1/genetics
• HIV-1/pathogenicity
• Humans
• RNA Splice Sites
• RNA Splicing
• RNA, Messenger
• RNA, Viral/genetics
• Virus Replication/genetics
• gag Gene Products, Human Immunodeficiency Virus/genetics

• antiviral immunity
• endogenous retroviruses
• sensing

• Animals
• Endogenous Retroviruses/genetics
• Endogenous Retroviruses/physiology
• Enhancer Elements, Genetic
• Gene Expression Regulation
• Humans
• Immunity, Cellular
• Promoter Regions, Genetic
• RNA, Double-Stranded/genetics
• RNA, Double-Stranded/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Viral/genetics
• RNA, Viral/metabolism
• Receptors, Pattern Recognition/metabolism
• Receptors, Virus/antagonists & inhibitors
• Receptors, Virus/metabolism
• Retroelements
• Viral Proteins/metabolism
• Virion/metabolism
• Virus Diseases/genetics
• Virus Diseases/immunology
• Virus Diseases/virology

• International Graduate School in Molecular Medicine Ulm
• Deutsche Forschungsgemeinschaft (DFG)

• AIDS/HIV
• Drug screens
• Expression profiling
• T cells
• Therapeutics

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting. This study aims at performing a meta-analysis of RNA-Seq expression profiles in samples of HIV-1 infected CD4+ T cells compared to uninfected cells to assess consistently differentially expressed genes in the context of HIV-1 infection. We selected two studies (22 samples: 15 experimentally infected and 7 mock-infected). We found 208 differentially expressed genes in infected cells when compared to uninfected/mock-infected cells. This result had moderate overlap when compared to previous studies of HIV-1 infection transcriptomics, but we identified 64 genes already known to interact with HIV-1 according to the HIV-1 Human Interaction Database. A gene ontology (GO) analysis revealed enrichment of several pathways involved in immune response, cell adhesion, cell migration, inflammation, apoptosis, Wnt, Notch and ERK/MAPK signaling.

• gene ontology
• genomics
• infection
• latency
• pathway analysis
• transcriptomics

• CD4-Positive T-Lymphocytes/metabolism
• CD4-Positive T-Lymphocytes/virology
• Gene Expression Profiling
• Gene Ontology
• HIV Infections/genetics
• HIV Infections/metabolism
• HIV Infections/virology
• HIV-1/physiology
• Host-Pathogen Interactions
• Humans
• Transcriptome

• HIV-1
• HIV-1 latency
• HIV-1 oversplicing
• HIV-1 splicing

• Alternative Splicing
• Exons
• Gene Expression Regulation, Viral
• HIV-1/genetics
• Nucleic Acid Conformation
• RNA Splicing
• RNA, Messenger/chemistry
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA, Viral/chemistry
• RNA, Viral/genetics
• RNA, Viral/metabolism
• Regulatory Sequences, Nucleic Acid
• Virus Latency/genetics
• rev Gene Products, Human Immunodeficiency Virus/genetics
• rev Gene Products, Human Immunodeficiency Virus/metabolism

• U54 AI150470 NIAID NIH HHS
• UM1-AI126619 NIH HHS
• R01 AI117780 NIAID NIH HHS
• R01AI117780 NIH HHS
• U54-AI15047 NIH HHS
• UM1 AI126619 NIAID NIH HHS

• trans-splicing
• cancer
• gene therapy
• genetic disease
• infectious disease
• ribozyme-mediated trans-splicing
• spliceosome-mediated RNA trans-splicing (SMaRT)
• split intein-mediated trans-splicing

• Humans
• Inteins
• Proteins
• Trans-Splicing

• 25332 Cancer Research UK
• C63549/A25332 Cancer Research UK

• HIV
• Rev
• human
• immunodeficiency
• virus

• Animals
• Drug Discovery
• Gene Expression Regulation, Viral
• Gene Products, rev/chemistry
• Gene Products, rev/genetics
• Gene Products, rev/metabolism
• HIV/physiology
• HIV Infections/drug therapy
• HIV Infections/metabolism
• HIV Infections/virology
• Host-Pathogen Interactions
• Humans
• Structure-Activity Relationship
• Viral Proteins/chemistry
• Viral Proteins/genetics
• Viral Proteins/metabolism
• Virus Replication

• MR/R021562/1 Medical Research Council
• 209412/Z/17/Z Wellcome Trust
• Wellcome Trust
• MC_UU_12014/10 Medical Research Council
• MR/L019434/1 Medical Research Council
• John Fell Fund, University of Oxford
• Biotechnology and Biological Sciences Research Council
• Wellcome

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.

Alternative splicing is a key step in Human Immunodeficiency Virus type 1 (HIV-1) replication that is tightly regulated both temporally and spatially. More than 50 different transcripts can be generated from a single HIV-1 unspliced pre-messenger RNA (pre-mRNA) and a balanced proportion of unspliced and spliced transcripts is critical for the production of infectious virions. Understanding the mechanisms involved in the regulation of viral RNA is therefore of potential therapeutic interest. However, monitoring the regulation of alternative splicing events at a transcriptome-wide level during cell infection is challenging. Here we used the long-read cDNA sequencing developed by Oxford Nanopore Technologies (ONT) to explore in a quantitative manner the complexity of the HIV-1 transcriptome regulation in infected primary CD4+ T cells.

ONT reads mapping to the viral genome proved sufficiently long to span all possible splice junctions, even distant ones, and to be assigned to a total of 150 exon combinations. Fifty-three viral RNA isoforms, including 14 new ones were further considered for quantification. Relative levels of viral RNAs determined by ONT sequencing showed a high degree of reproducibility, compared favourably to those produced in previous reports and highly correlated with quantitative PCR (qPCR) data. To get further insights into alternative splicing regulation, we then compiled quantifications of splice site (SS) usage and transcript levels to build “splice trees”, a quantitative representation of the cascade of events leading to the different viral isoforms. This approach allowed visualizing the complete rewiring of SS usages upon perturbation of SS D2 and its impact on viral isoform levels. Furthermore, we produced the first dynamic picture of the cascade of events occurring between 12 and 24 h of viral infection. In particular, our data highlighted the importance of non-coding exons in viral RNA transcriptome regulation.

ONT sequencing is a convenient and reliable strategy that enabled us to grasp the dynamic of the early splicing events modulating the viral RNA landscape in HIV-1 infected cells.

• Alternative splicing
• HIV RNA
• ONT long-read sequencing
• Viral transcriptome

• Aberrant proliferation
• Antigen-driven proliferation
• Chromatin accessibility
• Clonal expansion
• Defective HIV-1 proviruses
• HIV-1 cure
• HIV-1 integration site
• HIV-1 latent reservoir
• HIV-1 proviral landscape
• Homeostatic proliferation

• HERV-K
• HERV-K RcRE
• HIV RRE
• HIV Rev
• HIV-1
• Human endogenous retroviruses
• RNA export

• Endogenous Retroviruses/genetics
• Gene Expression Regulation, Viral
• Genome, Human
• HEK293 Cells
• HIV-1/genetics
• Humans
• Proviruses/genetics
• RNA, Viral/genetics
• rev Gene Products, Human Immunodeficiency Virus/genetics
• rev Gene Products, Human Immunodeficiency Virus/metabolism

• K08 AI136671 NIAID NIH HHS
• R21 AI134208 NIAID NIH HHS
• P30 CA044579 NCI NIH HHS
• AI134208 NIH HHS
• CA44579 NCI NIH HHS
• R01 CA206275 NCI NIH HHS
• CA206275 NIH HHS
• National Institutes of Health
• National Cancer Institute

Although human protein complexes have been reported to be directly related to viral infection, previous studies have not systematically investigated human-virus PPIs from the perspective of human protein complexes. To the best of our knowledge, we have presented here the most comprehensive and in-depth analysis of human-virus PPIs in the context of VTCs. Our findings confirm that human protein complexes are heavily involved in viral infection. The observed preferences of virally targeted subunits within complexes reflect the mechanisms used by viruses to manipulate host protein complexes. The identified periodic expression patterns of the VTCs and the corresponding candidates could increase our understanding of how viruses manipulate the host cell cycle. Finally, our proposed conceptual application framework of VTCs and the developed VTcomplex could provide new hints to develop antiviral drugs for the clinical treatment of viral infections.

Computational analysis of human-virus protein-protein interaction (PPI) data is an effective way toward systems understanding the molecular mechanism of viral infection. Previous work has mainly focused on characterizing the global properties of viral targets within the entire human PPI network. In comparison, how viruses manipulate host local networks (e.g., human protein complexes) has been rarely addressed from a computational perspective. By mainly integrating information about human-virus PPIs, human protein complexes, and gene expression profiles, we performed a large-scale analysis of virally targeted complexes (VTCs) related to five common human-pathogenic viruses, including influenza A virus subtype H1N1, human immunodeficiency virus type 1, Epstein-Barr virus, human papillomavirus, and hepatitis C virus. We found that viral targets are enriched within human protein complexes. We observed in the context of VTCs that viral targets tended to have a high within-complex degree and to be scaffold and housekeeping proteins. Complexes that are essential for viral propagation were simultaneously targeted by multiple viruses. We characterized the periodic expression patterns of VTCs and provided the corresponding candidates that may be involved in the manipulation of the host cell cycle. As a potential application of the current analysis, we proposed a VTC-based antiviral drug target discovery strategy. Finally, we developed an online VTC-related platform known as VTcomplex (http://zzdlab.com/vtcomplex/index.php or http://systbio.cau.edu.cn/vtcomplex/index.php). We hope that the current analysis can provide new insights into the global landscape of human-virus PPIs at the VTC level and that the developed VTcomplex will become a vital resource for the community.

IMPORTANCE Although human protein complexes have been reported to be directly related to viral infection, previous studies have not systematically investigated human-virus PPIs from the perspective of human protein complexes. To the best of our knowledge, we have presented here the most comprehensive and in-depth analysis of human-virus PPIs in the context of VTCs. Our findings confirm that human protein complexes are heavily involved in viral infection. The observed preferences of virally targeted subunits within complexes reflect the mechanisms used by viruses to manipulate host protein complexes. The identified periodic expression patterns of the VTCs and the corresponding candidates could increase our understanding of how viruses manipulate the host cell cycle. Finally, our proposed conceptual application framework of VTCs and the developed VTcomplex could provide new hints to develop antiviral drugs for the clinical treatment of viral infections.

• antiviral drug discovery
• human-virus interaction
• network
• protein complex
• protein-protein interaction

• HIV
• cure
• immune evasion
• immunotherapy
• latency
• remission
• transcription

Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research.

• Clonal expansion
• HIV persistence
• HIV reservoirs
• Proviral integration

• CD4-Positive T-Lymphocytes/metabolism
• CD4-Positive T-Lymphocytes/virology
• Clone Cells
• Gene Expression Profiling
• HIV-1/physiology
• Humans
• Principal Component Analysis
• RNA, Viral/metabolism
• Sequence Analysis, RNA
• Single-Cell Analysis
• Virus Latency/physiology

• UM1 AI126620 NIAID NIH HHS
• R01 AI037526 NIAID NIH HHS
• P01 AI100148 NIAID NIH HHS
• R37 AI037526 NIAID NIH HHS
• U01 AI118536 NIAID NIH HHS
• Howard Hughes Medical Institute
• UM1 AI100663 NIAID NIH HHS
• T32 AI070084 NIAID NIH HHS

• Internal Ribosome Entry Sites
• Protein Biosynthesis
• Viral Proteins/genetics
• Viral Proteins/metabolism
• Viruses/genetics

• Antiretroviral therapy
• Cell-associated HIV RNA
• HIV cure
• HIV persistence
• HIV reservoir
• Virological biomarker

• CpG dinucleotide
• Genomic RNA
• HIV-1
• Viral replication

HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes. Overexpression of BACH2 or STAT5B in primary T regulatory cells increases their proliferation and survival without compromising their function. Hence, we provide evidence that HIV-1-mediated insertional activation of BACH2 and STAT5B favor the persistence of a viral reservoir in T regulatory cells in patients under combination antiretroviral therapy.

HIV insertions in hematopoietic cells are enriched in BACH2 or MLK2 genes, but the selective advantages conferred are unknown. Here, the authors show that BACH2 and additionally STAT5B are activated by viral insertions, generating chimeric mRNAs specifically enriched in T regulatory cells favoring their persistence.

• HIV
• RNA metabolism
• SR proteins
• alternative splicing
• eukaryotic gene expression

• HIV
• HSV-tk/GCV
• RNA splicing
• RNA trans-splicing
• exon replacement
• gene therapy
• herpes simplex virus thymidine kinase-ganciclovir

• G0800142 Medical Research Council
• MC_PC_15042 Medical Research Council

• HIV
• eukaryotic gene expression
• mRNA translation

• COPD
• HIV
• inflammation
• lung cancer
• pulmonary hypertension

Measuring the altered gene expression level and identifying differentially expressed genes/proteins during HIV infection, replication and latency is fundamental for broadening our understanding of the mechanisms of HIV infection and T-cell dysfunction. Such studies are crucial for developing effective strategies for virus eradication from the body. Inspired by the availability and enrichment of gene expression data during HIV infection, replication and latency, in this study, we proposed a novel compendium termed HIVed (HIV expression database; http://hivlatency.erc.monash.edu/) that harbours comprehensive functional annotations of proteins, whose genes have been shown to be dysregulated during HIV infection, replication and latency using different experimental designs and measurements. We manually curated a variety of third-party databases for structural and functional annotations of the protein entries in HIVed. With the goal of benefiting HIV related research, we collected a number of biological annotations for all the entries in HIVed besides their expression profile, including basic protein information, Gene Ontology terms, secondary structure, HIV-1 interaction and pathway information. We hope this comprehensive protein-centric knowledgebase can bridge the gap between the understanding of differentially expressed genes and the functions of their protein products, facilitating the generation of novel hypotheses and treatment strategies to fight against the HIV pandemic.

• HIV-1
• RNA splicing
• next-generation sequencing
• primer ID
• simian immunodeficiency virus

• HIV
• PP2A
• Vif
• human
• infectious disease
• lentivirus
• microbiology
• phosphorylation
• proteomics

• Cells, Cultured
• HIV/physiology
• HIV Infections/pathology
• Host-Pathogen Interactions
• Humans
• Phosphoproteins/analysis
• Proteome/analysis
• Proteomics
• Time Factors
• vif Gene Products, Human Immunodeficiency Virus/metabolism

• Wellcome Trust
• 093964/Z/10/Z Wellcome Trust
• 101835/Z/13/Z Wellcome Trust

Eradication of human immunodeficiency virus (HIV) in infected individuals is currently not possible because of the presence of the persistent cellular reservoir of latent infection. The identification of HIV latency biomarkers and a better understanding of the molecular mechanisms contributing to regulation of HIV expression might provide essential tools to eliminate these latently infected cells. This review aims at summarizing gene expression profiling and systems biology applications to studies of HIV latency and eradication. Studies comparing gene expression in latently infected and uninfected cells identify candidate latency biomarkers and novel mechanisms of latency control. Studies that profiled gene expression changes induced by existing latency reversing agents (LRAs) highlight uniting themes driving HIV reactivation and novel mechanisms that contribute to regulation of HIV expression by different LRAs. Among the reviewed gene expression studies, the common approaches included identification of differentially expressed genes and gene functional category assessment. Integration of transcriptomic data with other biological data types is presently scarce, and the field would benefit from increased adoption of these methods in future studies. In addition, designing prospective studies that use the same methods of data acquisition and statistical analyses will facilitate a more reliable identification of latency biomarkers using different model systems and the comparison of the effects of different LRAs on host factors with a role in HIV reactivation. The results from such studies would have the potential to significantly impact the process by which candidate drugs are selected and combined for future evaluations and advancement to clinical trials.

• Gene expression
• Microarrays
• RNA-Seq
• Systems biology
• Human immunodeficiency virus
• Viral latency
• Disease eradication
• Biomarkers
• Molecular mechanisms
• Latency reversing agents