Could differential virological characteristics account for ongoing viral replication and insidious damage of the brain during HIV 1 infection of the central nervous system?

Vissers, Marloes; Stelma, F.F.; Koopmans, P.P.

doi:10.1016/j.jcv.2010.08.001

Cited by 11 publications

(8 citation statements)

References 99 publications

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“…CXCR4-using SHIVs have also been shown to cause an encephalitis in rhesus macaques [65]. Anti-retroviral therapy induces HIV to switch from co-receptor CCR5 to CXCR4 usage and this switch may appear later in the CNS compartment compared to the periphery [66]. In general, a switch from R5 to R5X4 or X4 is associated with acceleration of disease progression [60].…”

Section: Discussionmentioning

confidence: 99%

Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4

Anderson

Jaeger

et al. 2015

Aids

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Objectives HIV reservoir in the brain represents a major barrier for curing HIV infection. As the most abundant, long-lived cell type, astrocytes play a critical role in maintaining the reservoir; however the mechanism of infection remains unknown. Here, we determine how viral transmission occurs from HIV-infected lymphocytes to astrocytes by cell-to-cell contact. Design and methods Human astrocytes were exposed to HIV-infected lymphocytes and monitored by live-imaging, confocal microscopy, transmission and 3-demensional electron microscopy. A panel of receptor antagonists was used to determine mechanism of viral entry. Results We found that cell-to-cell contact resulted in efficient transmission of X4- or X4R5-using viruses from T lymphocytes to astrocytes. In co-cultures of astrocytes with HIV-infected lymphocytes, the interaction occurred through a dynamic process of attachment and detachment of the two cell types. Infected lymphocytes invaginated into astrocytes or the contacts occurred via filopodial extensions from either cell type, leading to formation of virological synapses. In the synapses, budding of immature or incomplete HIV particles from lymphocytes occurred directly onto the membranes of astrocytes. This cell-to-cell transmission could be almost completely blocked by anti-CXCR4 antibody and its antagonist, but only partially inhibited by CD4, ICAM1 antibodies. Conclusion Cell-to-cell transmission was mediated by a unique mechanism by which immature viral particles initiated a fusion process in a CXCR4-dependent, CD4-independent manner. These observations have important implications for developing approaches to prevent formation of HIV reservoirs in the brain.

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Section: Discussionmentioning

confidence: 99%

Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4

Anderson

Jaeger

et al. 2015

Aids

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“…Combined ART puts evolutionary pressure on the virus such that it evolves from using co-receptor CCR5 to co-receptor CXCR4. This switch may appear later in the CNS compartment compared to the periphery [42]. Further even in patients on antiretrovirals analysis of HIV-1 nef, gp120, and gp41 sequences showed maximal viral evolution within brain tissues of individuals with HAD compared with non-HAD cases [43].…”

Section: Timing Of Viral Entry Into the Brainmentioning

confidence: 99%

Where does HIV hide? A focus on the central nervous system

Churchill

Nath

2013

Current Opinion in HIV and AIDS

132

106

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Purpose of review To review the literature on infection and evolution of HIV within the brain in the context for understanding the nature of the brain reservoir and its consequences. Recent findings HIV-1 in the brain can evolve in separate compartments within macrophage/microglia and astrocytes. The virus adapts to the brain environment to infect these cells and brain-specific mutations can be found in nearly all genes of the virus. The virus evolves to become more neurovirulent. Summary The brain is an ideal reservoir for the HIV. The brain is a relatively immune privileged site and the blood–brain barrier prevents easy access to antiretroviral drugs. Further, the virus infects resident macrophages and astrocytes which are long-lived cells and causes minimal cytopathology in these cells. Hence as we move towards developing strategies for eradication of the virus from the peripheral reservoirs, it is critical that we pay close attention to the virus in the brain and develop strategies for maintaining it in a latent state failure of which could result in dire consequences.

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“…Findings in the literature to date are mixed, 88,89 although a high level of genetic diversity suggesting autonomous viral replication in the CNS has been associated with a low CPE score. 90 An adjusted CPE score has been proposed, to take into account drug resistance mutations in the CSF.…”

Section: Introductionmentioning

confidence: 99%

Controversies in HIV-associated neurocognitive disorders

Nightingale

Winston

Letendre

et al. 2014

The Lancet Neurology

260

197

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Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would benefit from routine screening for cognitive difficulties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated.

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Could differential virological characteristics account for ongoing viral replication and insidious damage of the brain during HIV 1 infection of the central nervous system?

Cited by 11 publications

References 99 publications

Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4

Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4

Where does HIV hide? A focus on the central nervous system

Controversies in HIV-associated neurocognitive disorders

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