HIV-1 Entry and Trans-Infection of Astrocytes Involves CD81 Vesicles

Gray, Lachlan Robert; Turville, Stuart; Hitchen, Tina L.; Cheng, Wan Jung; Ellett, Anne; Salehiniya, Hamid; Roche, Michael; Wesselingh, Steve Lodewyk; Gorry, Paul R; Churchill, Melissa

doi:10.1371/journal.pone.0090620

Cited by 60 publications

(62 citation statements)

References 48 publications

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“…First, astrocytes can be directly infected. For example, up to 19% of astroglial cells in post-mortem specimens obtained from HIV-1 patients contain viral genetic material and hence act as an infectious reservoir (Gray et al ., 2014; Joseph et al ., 2015; Narasipura et al ., 2014). Astrocytes have been found to accumulate HIV-1 within Cluster of Differentiation 81(CD81)-lined vesicles; as long as the virus remained in these vesicles it had protected from degradation.…”

Section: Infectious Diseases Of the Cnsmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

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Section: Infectious Diseases Of the Cnsmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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“…Astrocytes were shown to support HIV infection in both in vivo and in vitro studies, with the human mannose receptor reported to be essential for CD4-independent infection of this cell type [75,76]. However, more recent studies reported inconsistent findings regarding HIV infection of astrocytes and suggest that infection of astrocytes is highly restricted, may involve CD81 vesicles and may internalize virus particles without productive virus replication [77,78]. Regardless, the overall findings indicate that astrocyte infection or internalization lead to cellular dysfunction and facilitate transfer and dissemination of HIV-1 within the CNS.…”

Section: Cell Reservoirs Of Fivmentioning

confidence: 99%

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Eckstrand

Sparger

Murphy

2017

Journal of General Virology

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Infection with feline immunodeficiency virus (FIV), a lentivirus similar to human immunodeficiency virus (HIV), results in lifelong viral persistence and progressive immunopathology in the cat. FIV has the ability to infect and produce infectious virus in a number of different cell types. FIV provirus can also be maintained in a replication-competent but transcriptionally quiescent state, facilitating viral persistence over time. Immediately after the initial infection, FIV infection quickly disseminates to many anatomical compartments within the host including lymphoid organs, gastrointestinal tract and brain. Collectively, the anatomic and cellular compartments that harbour FIV provirus constitute the viral reservoir and contain foci of both ongoing viral replication and transcriptionally restricted virus that may persist over time. The relative importance of the different phenotypes observed for infected cells, anatomic compartment, replication status and size of the reservoir represent crucial areas of investigation for developing effective viral suppression and eradication therapies. In this review, we discuss what is currently known about FIV reservoirs, and emphasize the utility of the FIV-infected cat as a model for the HIV-infected human.

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“…Recent work by our group has highlighted the potential of HIV-1 to enter astrocytes via CD81-lined vesicles, bypassing the traditional CD4/coreceptor-dependent entry mechanisms [50]. Furthermore, these same compartments may play a role in viral dissemination within the CNS, via cell-to-cell spread, thereby potentially rendering entry inhibitors less effective [50].…”

Section: Obstacles If the Cns Is A Viral Reservoirmentioning

confidence: 99%

“…Furthermore, these same compartments may play a role in viral dissemination within the CNS, via cell-to-cell spread, thereby potentially rendering entry inhibitors less effective [50]. The altered transcriptional activity of CNS-derived LTRs suggest that activation strategies designed against T cell reservoirs may be ineffective at inducing CNS reservoirs [45-47].…”

Section: Obstacles If the Cns Is A Viral Reservoirmentioning

confidence: 99%

Is the central nervous system a reservoir of HIV-1?

Gray¹,

Roche²,

Flynn³

et al. 2014

Current Opinion in HIV and AIDS

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108

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Purpose of the review To summarize the evidence in the literature that supports the CNS as a viral reservoir for HIV-1 and to prioritise future research efforts. Recent findings HIV-1 DNA has been detected in brain tissue of patients with undetectable viral load or neurocognitive disorders, and is associated with long-lived cells such as astrocytes and microglia. In neurocognitively normal patients, HIV-1 can be found at high frequency in these cells (4% of astrocytes and 20% of macrophages). CNS cells have unique molecular mechanisms to suppress viral replication and induce latency, which include increased expression of dominant negative transcription factors and suppressive epigenetic factors. There is also evidence of continued inflammation in patients lacking a CNS viral load, suggesting the production and activity of viral neurotoxins (for example Tat). Summary Together, these findings provide evidence that the CNS can potentially act as a viral reservoir of HIV-1. However, the majority of these studies were performed in historical cohorts (absence of cART or presence of viral load) which do not reflect modern day patients (cART-treated and undetectable viral load). Future studies will need to examine patient samples with these characteristics to conclusively determine if the CNS represents a relevant and important viral reservoir.

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HIV-1 Entry and Trans-Infection of Astrocytes Involves CD81 Vesicles

Cited by 60 publications

References 48 publications

Translational potential of astrocytes in brain disorders

Translational potential of astrocytes in brain disorders

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

Is the central nervous system a reservoir of HIV-1?

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