ArticleJournal of neurovirology2011
Genetic and functional heterogeneity of CNS-derived tat alleles from patients with HIV-associated dementia.
Article in Journal of neurovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- A naturally occurring Tat R52W variant in brain-derived HIV attenuates transcription and may contribute to reservoir persistence.bioRxiv : the preprint server for biology · 2026Article
- Retrospective Observational Study of CSF-Derived HIV-1 Tat and Vpr Amino Acid Sequences in a South African Pediatric Cohort with HIV Subtype C.International journal of molecular sciences · 2025Observational
- Self-reported neurocognitive complaints in the Swiss HIV Cohort Study: a viral genome-wide association study.Brain communications · 2024Article
- Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence.International journal of molecular sciences · 2023Article
- Shock and kill within the CNS: A promising HIV eradication approach?Journal of leukocyte biology · 2022Review
- Review
- HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Article
- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Article
- HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection.Journal of acquired immune deficiency syndromes (1999) · 2017Article
- Eradication of human immunodeficiency virus from brain reservoirs.Journal of neurovirology · 2015Review
- HIV migration between blood and cerebrospinal fluid or semen over time.The Journal of infectious diseases · 2014Article
- Defining differential genetic signatures in CXCR4- and the CCR5-utilizing HIV-1 co-linear sequences.PloS one · 2014Article
- Monocytes mediate HIV neuropathogenesis: mechanisms that contribute to HIV associated neurocognitive disorders.Current HIV research · 2014Review
- Update on HIV-associated neurocognitive disorders.Current neurology and neuroscience reports · 2013Review
- HIV-1 Tat protein variants: critical role for the cysteine region in synaptodendritic injury.Experimental neurology · 2013Article
- Where does HIV hide? A focus on the central nervous system.Current opinion in HIV and AIDS · 2013Review
- Reduced basal transcriptional activity of central nervous system-derived HIV type 1 long terminal repeats.AIDS research and human retroviruses · 2013Article
- LRRK2 kinase inhibition prevents pathological microglial phagocytosis in response to HIV-1 Tat protein.Journal of neuroinflammation · 2012Article
- HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment.Cold Spring Harbor perspectives in medicine · 2012Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1) demonstrates a high degree of viral diversity which has an impact on viral fitness. Genetic compartmentalization of HIV-1 proteins between central nervous system (CNS) and lymphoid tissues is well established and reflects altered requirements for HIV-1 replication in macrophages/microglia, brain-specific immune selection pressures and possibly the timing of virus invasion of the CNS. Tat-encoding mRNA has been detected in the CNS of HIV-1 infected individuals and its neurotoxic effects in the CNS are well documented. However, while CNS-derived tat sequences have demonstrated significant diversity, the effect of this molecular diversity on transcriptional regulation and its impact on the pathogenesis of HIV-associated dementia (HAD) remains unclear. In this study, we cloned and characterised 44 unique tat alleles from brain, cerebral spinal fluid, spinal cord and blood/lymphoid tissue-derived HIV-1 isolates from five subjects with HAD. While phylogenetic analyses revealed tissue-specific compartmentalization of Tat variants for two patients, broad compartmentalization across the panel of tissue-derived viruses was not observed. Despite the lack of consistent tissue-specific compartmentalization, sequence variations within patients segregated CNS and non-CNS tat alleles. These amino acid alterations predominated within the transactivation domain of Tat and could account for alterations in the ability of particular Tat proteins to transactivate the LTR. Although a subset of patients demonstrated reduced transactivation capacity among CNS-derived Tat proteins compared to those from matched lymphoid tissues, overall Tat proteins from the CNS to lymphoid compartments maintained similar levels of transactivation function. Together, these data suggest that despite the observed heterogeneity in tat alleles isolated from matched lymphoid to CNS compartments, Tat function is maintained, highlighting the importance of Tat function in HIV-1 neuropathogenesis.
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