A5070916977- HIV Research and Treatment
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- NF-κB Signaling Pathways
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- HIV/AIDS Research and Interventions
- interferon and immune responses
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Adrenal Hormones and Disorders
- T-cell and Retrovirus Studies
- Mosquito-borne diseases and control
University of California, San Francisco
2014-2023
Ljubljana University Medical Centre
2023
University Medical Center
2023
University of Helsinki
2009-2013
Helsinki University Hospital
2013
University of Ljubljana
2003-2011
Universidad Católica de Santa Fe
2006
Harvard University
2003
Bipar
2003
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2003
The HIV accessory protein negative factor (Nef) is one of the earliest and most abundantly expressed viral proteins. It also found in serum infected individuals (Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C. Exosomal-like vesicles are present human blood plasma. Int Immunol 2005;17:879-887). Extracellular Nef has deleterious effects on CD4(+) T cells (James CO, Huang MB, Khan M, Garcia-Barrio Powell MD, Bond VC. targets for apoptosis by interacting with CXCR4 surface...
Various cyclin-dependent kinase (Cdk) complexes have been implicated in the regulation of transcription. In this study, we identified a 70-kDa Cyclin K (CycK) that binds Cdk12 and Cdk13 to form two different (CycK/Cdk12 or CycK/Cdk13) human cells. The CycK/Cdk12 complex regulates phosphorylation Ser2 C-terminal domain RNA polymerase II expression small subset genes, as revealed microarrays. Depletion results decreased predominantly long genes with high numbers exons. most prominent group...
Flavopiridol (L86-8275, HMR1275) is a cyclin-dependent kinase (Cdk) inhibitor that in clinical trials as cancer treatment because of its antiproliferative properties. We found the flavonoid potently inhibited transcription by RNA polymerase II <i>in vitro</i> blocking transition into productive elongation, step controlled P-TEFb. The ability P-TEFb to phosphorylate carboxyl-terminal domain large subunit was flavopiridol with a<i>K</i> <sub>i</sub> 3 nm. Interestingly, drug not competitive...
Recently, APOBEC3G has been identified as a host factor that blocks retroviral replication. It introduces G to A hypermutations in newly synthesized minus strand viral cDNA at the step of reverse transcription target cells. Here, we human APOBEC3F protein another immunodeficiency virus type 1 (HIV-1) Similar APOBEC3G, also induced HIV genomic DNA, and Vif counteracted its activity. Thus, APOBEC family members might have evolved general defense mechanism body against retroviruses,...
The human immunodeficiency virus (HIV-1)-encoded trans-activator (tat) increases HIV gene expression and replication. Previously, we demonstrated that tat facilitates elongation of transcription through the HIV-1 long terminal repeat (LTR) short transcripts corresponding to prematurely terminated RNA are released accumulate in absence tat. Here, using a transient assay, tested clustered compensatory mutations, as well 3' deletions, trans-acting responsive region (tar) observed primary...
The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies purge these reservoirs are needed and activation viral gene expression one promising strategy. Bromodomain Extraterminal (BET) bromodomain inhibitors (BETi) compounds able reactivate latent proviruses positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential protein kinase C...
The elongation of transcription is a highly regulated process that requires negative and positive effectors. By binding the double-stranded stem in transactivation response (TAR) element, RD protein from factor (NELF) inhibits basal long terminal repeat human immunodeficiency virus type 1 (HIVLTR). Tat its cellular cofactor, b (P-TEFb), overcome this effect. Cdk9 P-TEFb also phosphorylates at sites next to RNA recognition motif. A mutant mimics phosphorylated form no longer binds TAR nor...
The genome of human immunodeficiency virus encodes a protein that dramatically elevates amounts viral proteins. precise mechanism this trans-activation remains to be established. It has been reported can occur without major changes in the levels mRNA. We constructed recombinant plasmids containing those sequences required cis for linked chloramphenicol acetyltransferase gene. These were introduced into cultured cells either presence or absence second plasmid directed expression...
Human immunodeficiency virus (HIV), the causative agent of AIDS, infects and kills lymphoid cells bearing CD4 antigen. In an infected cell, a number cellular as well HIV-encoded gene products determine levels viral expression HIV replication. Efficient HIV-replication occurs in activated T cells. Utilizing transient assays, we show that directed by long terminal repeat (LTR) increases response to T-cell activation signals. The effects trans-activator (TAT) are multiplicative. Analysis...
With T-cell lines constitutively expressing Nef from the SF2 strain of human immunodeficiency virus type 1 (HIV-1SF2) in form a hybrid CD8-Nef fusion protein or chronically infected with HIV-1SF2, cellular serine kinase was found that specifically associates Nef. Proteins 62 kDa and 72 kDa, which coimmunoprecipitated Nef, were phosphorylated vitro assays. This Nef-associated activity not blocked by inhibitors C A lost when truncated at amino acid 94 99. These findings present evidence is...
Human immunodeficiency virus 1 has been implicated as the main etiologic agent of acquired syndrome. However, other infectious agents may accelerate progression this disease. In particular, hepatitis B suggested one such cofactor. Therefore, we have investigated effects gene products on expression human I in transient transfection studies Jurkat lymphoblastic T cells, using reporter chloramphenicol acetyltransferase coupled to long terminal repeat I. As measured by amount activity, directed...
Hexamethylene bisacetamide (HMBA) is a potent inducer of cell differentiation and HIV production in chronically infected cells. However, its mechanism action remains poorly defined. In this study, we demonstrate that HMBA activates transiently the PI3K/Akt pathway, which leads to phosphorylation HEXIM1 subsequent release active positive transcription elongation factor b (P-TEFb) from transcriptionally inactive complex with 7SK small nuclear RNA (snRNA). As result, P-TEFb recruited promoter...
The human immunodeficiency virus encodes the transcriptional transactivator Tat, which binds to transactivation response (TAR) RNA stem–loop in viral long terminal repeat (LTR) and increases rates of elongation rather than initiation transcription by polymerase II (Pol II). In this study, we demonstrate that Tat directly cyclin-dependent kinase 7 (CDK7), leads productive interactions between CDK-activating (CAK) complex TFIIH. activates phosphorylation carboxy-terminal domain (CTD) Pol CAK...