New Challenges of HIV-1 Infection: How HIV-1 Attacks and Resides in the Central Nervous System

Rojas-Celis, Victoria; Valiente-Echeverría, Fernando; Soto-Rifo, Ricardo; Toro-Ascuy, Daniela

doi:10.3390/cells8101245

Cited by 58 publications

(44 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The secreted Tat can be passed into uninfected cells, where it can render the cells more susceptible to infection [134], disrupt immune response by inducing apoptosis of T lymphocytes [135], and down-modulate expression of MHC class I [136]. In addition, the secreted Tat can traffic to the central nervous system by crossing the blood-brain barrier [137], where it plays a role in HIV-associated neurocognitive disorders [138,139].…”

Section: Anti-tat Vaccines That May Compliment Cartmentioning

confidence: 99%

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Jin

Lin

et al. 2020

Viruses

View full text Add to dashboard Cite

The human immunodeficiency virus type 1 (HIV) establishes a chronic infection that can be well controlled, but not cured, by combined antiretroviral therapy (cART). Interventions have been explored to accomplish a functional cure, meaning that a patient remains infected but HIV is undetectable in the blood, with the aim of allowing patients to live without cART. Tat, the viral transactivator of transcription protein, plays a critical role in controlling HIV transcription, latency, and viral rebound following the interruption of cART treatment. Therefore, a logical approach for controlling HIV would be to block Tat. Tackling Tat with inhibitors has been a difficult task, but some recent discoveries hold promise. Two anti-HIV proteins, Nullbasic (a mutant of Tat) and HT1 (a fusion of HEXIM1 and Tat functional domains) inhibit viral transcription by interfering with the interaction of Tat and cellular factors. Two small molecules, didehydro-cortistatin A (dCA) and triptolide, inhibit Tat by different mechanisms: dCA through direct binding and triptolide through enhanced proteasomal degradation. Finally, two Tat-based vaccines under development elicit Tat-neutralizing antibodies. These vaccines have increased the levels of CD4+ cells and reduced viral loads in HIV-infected people, suggesting that the new vaccines are therapeutic. This review summarizes recent developments of anti-Tat agents and how they could contribute to a functional cure for HIV.

show abstract

Section: Anti-tat Vaccines That May Compliment Cartmentioning

confidence: 99%

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Jin

Lin

et al. 2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Human immunodeficiency virus (HIV) still remains one of the challenges for humanity (Rojas-Celis et al, 2019 ; Tarasova et al, 2020 ). The number of new HIV cases per year reached 1.7 million (WHO, HIV incidence) 1 while is, Number of People (All Ages) Living With HIV 2 is around 38 million (WHO).…”

Section: Introductionmentioning

confidence: 99%

Automated Extraction of Information From Texts of Scientific Publications: Insights Into HIV Treatment Strategies

et al. 2020

View full text Add to dashboard Cite

Text analysis can help to identify named entities (NEs) of small molecules, proteins, and genes. Such data are very important for the analysis of molecular mechanisms of disease progression and development of new strategies for the treatment of various diseases and pathological conditions. The texts of publications represent a primary source of information, which is especially important to collect the data of the highest quality due to the immediate obtaining information, in comparison with databases. In our study, we aimed at the development and testing of an approach to the named entity recognition in the abstracts of publications. More specifically, we have developed and tested an algorithm based on the conditional random fields, which provides recognition of NEs of (i) genes and proteins and (ii) chemicals. Careful selection of abstracts strictly related to the subject of interest leads to the possibility of extracting the NEs strongly associated with the subject. To test the applicability of our approach, we have applied it for the extraction of (i) potential HIV inhibitors and (ii) a set of proteins and genes potentially responsible for viremic control in HIV-positive patients. The computational experiments performed provide the estimations of evaluating the accuracy of recognition of chemical NEs and proteins (genes). The precision of the chemical NEs recognition is over 0.91; recall is 0.86, and the F1-score (harmonic mean of precision and recall) is 0.89; the precision of recognition of proteins and genes names is over 0.86; recall is 0.83; while F1-score is above 0.85. Evaluation of the algorithm on two case studies related to HIV treatment confirms our suggestion about the possibility of extracting the NEs strongly relevant to (i) HIV inhibitors and (ii) a group of patients i.e., the group of HIV-positive individuals with an ability to maintain an undetectable HIV-1 viral load overtime in the absence of antiretroviral therapy. Analysis of the results obtained provides insights into the function of proteins that can be responsible for viremic control. Our study demonstrated the applicability of the developed approach for the extraction of useful data on HIV treatment.

show abstract

“…HIV-infected monocytes/macrophages or CD4+ T-cells can cross the BBB and release virions or viral proteins that may negatively impact other cells types in the brain (Valcour et al, 2011 ). Perivascular macrophages and microglia are the primary cell types in the CNS that are infected by HIV-1 and support productive viral replication (Rojas-Celis et al, 2019 ). Neurons and oligodendrocytes are not believed to be infected by HIV-1.…”

Section: Astrocytes and Hivmentioning

confidence: 99%

Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management?

Tice¹,

McDevitt

Langford³

2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The discovery of the glial-lymphatic or glymphatic fluid clearance pathway in the rodent brain led researchers to search for a parallel system in humans and to question the implications of this pathway in neurodegenerative diseases. Magnetic resonance imaging studies revealed that several features of the glymphatic system may be present in humans. In both rodents and humans, this pathway promotes the exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF) through the arterial perivascular spaces into the brain parenchyma. This process is facilitated in part by aquaporin-4 (AQP4) water channels located primarily on astrocytic end feet that abut cerebral endothelial cells of the blood brain barrier. Decreased expression or mislocalization of AQP4 from astrocytic end feet results in decreased interstitial flow, thereby, promoting accumulation of extracellular waste products like hyperphosphorylated Tau (pTau). Accumulation of pTau is a neuropathological hallmark in Alzheimer's disease (AD) and is accompanied by mislocalization of APQ4 from astrocyte end feet to the cell body. HIV infection shares many neuropathological characteristics with AD. Similar to AD, HIV infection of the CNS contributes to abnormal aging with altered AQP4 localization, accumulation of pTau and chronic neuroinflammation. Up to 30% of people with HIV (PWH) suffer from HIV-associated neurocognitive disorders (HAND), and changes in AQP4 may be clinically important as a contributor to cognitive disturbances. In this review, we provide an overview and discussion of the potential contributions of NeuroHIV to glymphatic system functions by focusing on astrocytes and AQP4. Although HAND encompasses a wide range of neurocognitive impairments and levels of neuroinflammation vary among and within PWH, the potential contribution of disruption in AQP4 may be clinically important in some cases. In this review we discuss implications for possible AQP4 disruption on NeuroHIV disease trajectory and how HIV may influence AQP4 function.

show abstract

New Challenges of HIV-1 Infection: How HIV-1 Attacks and Resides in the Central Nervous System

Cited by 58 publications

References 112 publications

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Automated Extraction of Information From Texts of Scientific Publications: Insights Into HIV Treatment Strategies

Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management?

Contact Info

Product

Resources

About