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HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS

Overview of attention for article published in Journal of Neuroinflammation, March 2016
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Title
HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS
Published in
Journal of Neuroinflammation, March 2016
DOI 10.1186/s12974-016-0510-1
Pubmed ID
Authors

Joan W. Berman, Loreto Carvallo, Clarisa M. Buckner, Aimée Luers, Lisa Prevedel, Michael V. Bennett, Eliseo A. Eugenin

Abstract

HIV-associated neurocognitive disorders (HAND) are a major complication in at least half of the infected population despite effective antiretroviral treatment and immune reconstitution. HIV-associated CNS damage is not correlated with active viral replication but instead is associated with mechanisms that regulate inflammation and neuronal compromise. Our data indicate that one of these mechanisms is mediated by gap junction channels and/or hemichannels. Normally, gap junction channels shutdown under inflammatory conditions, including viral diseases. However, HIV infection upregulates Connexin43 (Cx43) expression and maintains gap junctional communication by unknown mechanism(s). Human primary astrocytes were exposed to several HIV proteins as well as to HIV, and expression and function of Connexin43- and Connexin30-containing channels were determined by western blot, immunofluorescence, microinjection of a fluorescent tracer and chromatin immunoprecipitation (ChIP). Here, we demonstrate that HIV infection increases Cx43 expression in vivo. HIV-tat, the transactivator of the virus, and no other HIV proteins tested, increases Cx43 expression and maintains functional gap junctional communication in human astrocytes. Cx43 upregulation is mediated by binding of the HIV-tat protein to the Cx43 promoter, but not to the Cx30 promoter, resulting in increased Cx43 messenger RNA (mRNA) and protein as well as gap junctional communication. We propose that HIV-tat contributes to the spread of intracellular toxic signals generated in a few HIV-infected cells into surrounding uninfected cells by upregulating gap junctional communication. In the current antiretroviral era, where HIV replication is often completely suppressed, viral factors such as HIV-tat are still produced and released from infected cells. Thus, blocking the effects of HIV-tat could result in new strategies to reduce the damaging consequences of HIV infection of the CNS.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 2%
Unknown 41 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 19%
Researcher 7 17%
Student > Master 4 10%
Student > Bachelor 2 5%
Lecturer > Senior Lecturer 1 2%
Other 7 17%
Unknown 13 31%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 12%
Neuroscience 4 10%
Pharmacology, Toxicology and Pharmaceutical Science 4 10%
Medicine and Dentistry 4 10%
Nursing and Health Professions 3 7%
Other 6 14%
Unknown 16 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 March 2016.
All research outputs
#5,558,633
of 7,351,662 outputs
Outputs from Journal of Neuroinflammation
#684
of 948 outputs
Outputs of similar age
#197,151
of 280,860 outputs
Outputs of similar age from Journal of Neuroinflammation
#44
of 59 outputs
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So far Altmetric has tracked 948 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
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We're also able to compare this research output to 59 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.