Towards a cure for human immunodeficiency virus

Pitman, Matthew C.; Lewin, Sharon R.

doi:10.1111/imj.13673

Cited by 2 publications

(2 citation statements)

References 29 publications

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“…Current cure research is focused on T cells, the primary HIV reservoir. Cure strategies are varied and include CRISPR based gene therapy, vaccines to boost anti-HIV immune response, broadly neutralizing antibody immunotherapy approaches to cure, and the “shock and kill” strategy, in which the latent reservoir is targeted by reversing latency under continued suppressive cART and triggering cell death (170). This strategy is still in development and has seen limited success (171–178).…”

Section: Relevance Of the Monocyte/macrophage Reservoir For Hiv Cure mentioning

confidence: 99%

The HIV Reservoir in Monocytes and Macrophages

Jaworowski²,

2019

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In people living with HIV (PLWH) who are failing or unable to access combination antiretroviral therapy (cART), monocytes and macrophages are important drivers of pathogenesis and progression to AIDS. The relevance of the monocyte/macrophage reservoir in PLWH receiving cART is debatable as in vivo evidence for infected cells is limited and suggests the reservoir is small. Macrophages were assumed to have a moderate life span and lack self-renewing potential, but recent discoveries challenge this dogma and suggest a potentially important role of these cells as long-lived HIV reservoirs. This, combined with new HIV infection animal models, has led to a resurgence of interest in monocyte/macrophage reservoirs. Infection of non-human primates with myeloid-tropic SIV implicates monocyte/macrophage activation and infection in the brain with neurocognitive disorders, and infection of myeloid-only humanized mouse models are consistent with the potential of the monocyte/macrophage reservoir to sustain infection and be a source of rebound viremia following cART cessation. An increased resistance to HIV-induced cytopathic effects and a reduced susceptibility to some antiretroviral drugs implies macrophages may be relevant to residual replication under cART and to rebound viremia. With a reappraisal of monocyte circulation dynamics, and the development of techniques to differentiate between self-renewing tissue-resident, and monocyte-derived macrophages in different tissues, a new framework exists to contextualize and evaluate the significance and relevance of the monocyte/macrophage HIV reservoir. In this review, we discuss recent developments in monocyte and macrophage biology and appraise current and emerging techniques to quantify the reservoir. We discuss how this knowledge influences our evaluation of the myeloid HIV reservoir, the implications for HIV pathogenesis in both viremic and virologically-suppressed PLWH and the need to address the myeloid reservoir in future treatment and cure strategies.

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Section: Relevance Of the Monocyte/macrophage Reservoir For Hiv Cure mentioning

confidence: 99%

The HIV Reservoir in Monocytes and Macrophages

Jaworowski²,

2019

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“…Currently, reducing HIV mortality has made giant strides since the implementation of antiretroviral therapy, but the elimination of the integrated virus in its latent stage remains elusive [ 89 ]. To investigate HIV integration sites in host cells, a small panel comprising 52 baits to capture a 72 bp region in the U3 region was designed across 573 long terminal repeat sequences post-clustering (500-fold enrichment) [ 90 ].…”

Section: Hybrid-capture Target Enrichment For Pathogensmentioning

confidence: 99%

Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology

Quek,

2024

Pathogens

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High-throughput sequencing (HTS) has revolutionised the field of pathogen genomics, enabling the direct recovery of pathogen genomes from clinical and environmental samples. However, pathogen nucleic acids are often overwhelmed by those of the host, requiring deep metagenomic sequencing to recover sufficient sequences for downstream analyses (e.g., identification and genome characterisation). To circumvent this, hybrid-capture target enrichment (HC) is able to enrich pathogen nucleic acids across multiple scales of divergences and taxa, depending on the panel used. In this review, we outline the applications of HC in human pathogens—bacteria, fungi, parasites and viruses—including identification, genomic epidemiology, antimicrobial resistance genotyping, and evolution. Importantly, we explored the applicability of HC to clinical metagenomics, which ultimately requires more work before it is a reliable and accurate tool for clinical diagnosis. Relatedly, the utility of HC was exemplified by COVID-19, which was used as a case study to illustrate the maturity of HC for recovering pathogen sequences. As we unravel the origins of COVID-19, zoonoses remain more relevant than ever. Therefore, the role of HC in biosurveillance studies is also highlighted in this review, which is critical in preparing us for the next pandemic. We also found that while HC is a popular tool to study viruses, it remains underutilised in parasites and fungi and, to a lesser extent, bacteria. Finally, weevaluated the future of HC with respect to bait design in the eukaryotic groups and the prospect of combining HC with long-read HTS.

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Towards a cure for human immunodeficiency virus

Cited by 2 publications

References 29 publications

The HIV Reservoir in Monocytes and Macrophages

The HIV Reservoir in Monocytes and Macrophages

Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology

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