Despite the intense effort put by researchers globally to understand Human Immunodeficiency Virus (HIV-1) pathogenesis since its discovery 30 years ago, the acquired knowledge till date is not good enough to eradicate HIV-1 from an infected individual. HIV-1 infects cells of the human immune system and integrates into the host cell genome thereby leading to persistent infection in these cells. Based on the activation status of the cells, the infection could be productive or result in latent infection. The current regimen used to treat HIV-1 infection in an AIDS patient includes combination of antiretroviral drugs called Highly Active Anti-Retroviral Therapy (HAART). A major challenge for the success of HAART has been these latent reservoirs of HIV which remain hidden and pose major hurdle for the eradication of virus. Combination of HAART therapy with simultaneous activation of latent reservoirs of HIV-1 seems to be the future of anti-retroviral therapy; however, this will require a much better understanding of the mechanisms and regulation of HIV-1 latency. In this chapter, we have tried to elaborate on HIV-1 latency, highlighting the strategies employed by the virus to ensure persistence in the host with specific focus on epigenetic regulation of latency. A complete understanding of HIV-1 latency will be extremely essential for ultimate eradication of HIV-1 from the human host.
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http://dx.doi.org/10.1007/978-94-007-4525-4_21 | DOI Listing |
J Virol
January 2025
Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.
One key determinant of HIV-1 latency reversal is the activation of the viral long terminal repeat (LTR) by cellular transcription factors such as NF-κB and AP-1. Interestingly, the activity of these two transcription factors can be modulated by glucocorticoid receptors (GRs). Furthermore, the HIV-1 genome contains multiple binding sites for GRs.
View Article and Find Full Text PDFJ Virus Erad
December 2024
HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.
View Article and Find Full Text PDFCell Rep
January 2025
Gladstone Institutes, San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA. Electronic address:
We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4 T cells are not. In lymph node CD4 Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.
Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies.
View Article and Find Full Text PDFEpigenetics Chromatin
January 2025
Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
Despite significant advances in HIV treatment, a definitive cure remains elusive. The first-in-human clinical trial of Excision BioTherapeutics' CRISPR-based HIV cure, EBT-101, demonstrated safety but failed to prevent viral rebound. These outcomes may result from the interplay of several factors.
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