Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection

Killingsworth, Lauren; Spudich, Serena

doi:10.1007/s00281-022-00953-5

Cited by 12 publications

(13 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data indicate that both microglia/macrophages (Iba-1-positive cells) and a small population of astrocytes (GFAP-positive cells) contain integrated HIV DNA in the host DNA. Both populations remain stable within the CNS for years, probably due to the multiple mechanisms of survival triggers for HIV latency [ 28 , 30 , 88 , 89 , 90 ]. We demonstrated that both cell types could transfer infection into cells that support high replication, as described [ 31 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain

Donoso

D’Amico

Valdebenito

et al. 2022

Cells

View full text Add to dashboard Cite

The major barrier to cure HIV infection is the early generation and extended survival of HIV reservoirs in the circulation and tissues. Currently, the techniques used to detect and quantify HIV reservoirs are mostly based on blood-based assays; however, it has become evident that viral reservoirs remain in tissues. Our study describes a novel multi-component imaging method (HIV DNA, mRNA, and viral proteins in the same assay) to identify, quantify, and characterize viral reservoirs in tissues and blood products obtained from HIV-infected individuals even when systemic replication is undetectable. In the human brains of HIV-infected individuals under ART, we identified that microglia/macrophages and a small population of astrocytes are the main cells with integrated HIV DNA. Only half of the cells with integrated HIV DNA expressed viral mRNA, and one-third expressed viral proteins. Surprisingly, we identified residual HIV-p24, gp120, nef, vpr, and tat protein expression and accumulation in uninfected cells around HIV-infected cells suggesting local synthesis, secretion, and bystander uptake. In conclusion, our data show that ART reduces the size of the brain’s HIV reservoirs; however, local/chronic viral protein secretion still occurs, indicating that the brain is still a major anatomical target to cure HIV infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain

Donoso

D’Amico

Valdebenito

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…The third phase of HIV brain clinical pathology research emerged with the delineation of the common but less severe neurocognitive disorders (NCD), using clinical and psychometric tests, coinciding with more systematic investigations using neuroimaging and an increasing range of blood and CSF tests for not only HIV virus, but inflammatory biomarkers of NCD [ 17 ]. What is striking to a pathologist is how classical neuropathology, the microscopic histopathology of the brain, hardly features in this latest research.…”

Section: Three Phases Of Hiv Neuropathology Investigationmentioning

confidence: 99%

“…The focus is on examining CSF and blood fluids in parallel, studying HIV virus levels and cell tropisms, drug resistance, comparing CSF and blood lymphocyte counts, looking for biomarkers of brain inflammation, comparing different ART regimes, testing for compartmentalisation of HIV in the brain and viral escape, and all correlated with neuroimaging. The goal is to identify predictive biomarkers for NCD in CSF and, especially, in peripheral blood samples, and many patients have had been sampled sequentially over long periods of time [ 17 ]. This is evidently appropriate, since brain tissue sampling is increasingly difficult to include in research studies, for practical and ethical reasons.…”

Section: The Modern Neuropathology Of Hiv-associated Neurocognitive D...mentioning

confidence: 99%

“…For an exhaustive review of the results of this latest phase of HIV brain research, a recently published review is highly commended [ 17 ]. Conceptually it follows from the older pre-ART classic neuropathology and then later morphological studies quantifying HIV quantities and numbers of macrophages and microglia, and correlating these with pre-mortem dementia.…”

Section: The Modern Neuropathology Of Hiv-associated Neurocognitive D...mentioning

confidence: 99%

See 1 more Smart Citation

Historical and current issues in HIV encephalitis, and the role of neuropathology in HIV disease: a pathological perspective

Lucas

2022

J Neurol

View full text Add to dashboard Cite

In the 1980s, after the HIV pandemic was recognised, neuropathology identified cerebral white matter lesions that were found in the brains of infected persons with a severe irreversible dementia syndrome, this became known as ‘HIV encephalitis’. Subsequent work in Europe and north America found subtle morphological abnormalities in cerebral neurones and their connections. With the advent of effective anti-retroviral therapies after 1996, the incidence of severe HIV-related dementia declined, as did investigative tissue pathology into this HIV brain disease. Currently, the intense interest over HIV neurocognitive impairment focuses on neuroimaging, comparative blood and cerebrospinal fluid analysis, viral subtype analysis, and the search for biomarkers that correlate with brain function. Tissue neuropathology in HIV is more restricted to the diagnosis of acute disease such as opportunistic infections and tumours, and confirmation of the acute CD8 + T-cell encephalitis syndrome. But correlative tissue pathology will still be needed as newer therapeutic measures are developed to prevent and manage chronic HIV brain impairment.

show abstract

“…In contrast to cancer and glioblastoma, Killingsworth et al outline the neuropathogenesis of CNS viral infection by HIV from initial HIV entry into the CNS to chronic infection. 11 The review explores how chronic HIV infection is maintained in the CNS and how the virus remains in a latent "hidden" state in diverse cells in the brain leading to sustained pathological inflammatory responses. This can lead to persist of HIV and associate with ongoing neuropathology including CD8 + T-lymphocyte-mediated encephalitis.…”

Section: Neuroimmune Interactions In Health and Diseasementioning

confidence: 99%

Neuroimmune interactions in health and disease

Hafler

Sansing

2022

Semin Immunopathol

View full text Add to dashboard Cite

Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection

Cited by 12 publications

References 126 publications

Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain

Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain

Historical and current issues in HIV encephalitis, and the role of neuropathology in HIV disease: a pathological perspective

Neuroimmune interactions in health and disease

Contact Info

Product

Resources

About