Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging
Abstract The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the se...
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Nature Portfolio
2017
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oai:doaj.org-article:a9afe25e6dc247338322f014d0f673202021-12-02T12:32:46ZChronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging10.1038/s41598-017-07570-52045-2322https://doaj.org/article/a9afe25e6dc247338322f014d0f673202017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07570-5https://doaj.org/toc/2045-2322Abstract The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage. However, this assumption has never been experimentally tested. Here we take advantage of the leaky tetracycline promoter system in the Tat-transgenic mouse to show that a chronic very low-level expression of Tat is associated with astrocyte activation, inflammatory cytokine expression, ceramide accumulation, reductions in brain volume, synaptic, and axonal damage that occurs over a time frame of 1 year. These data suggest that a chronic low-level production of Tat may contribute to progressive neurological damage in virally suppressed HIV-infected individuals.Alex M. DickensSeung Wan YooAlfred C. ChinJiadi XuTory P. JohnsonAmanda L. TroutKurt F. HauserNorman J. HaugheyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q Alex M. Dickens Seung Wan Yoo Alfred C. Chin Jiadi Xu Tory P. Johnson Amanda L. Trout Kurt F. Hauser Norman J. Haughey Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging |
| description |
Abstract The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage. However, this assumption has never been experimentally tested. Here we take advantage of the leaky tetracycline promoter system in the Tat-transgenic mouse to show that a chronic very low-level expression of Tat is associated with astrocyte activation, inflammatory cytokine expression, ceramide accumulation, reductions in brain volume, synaptic, and axonal damage that occurs over a time frame of 1 year. These data suggest that a chronic low-level production of Tat may contribute to progressive neurological damage in virally suppressed HIV-infected individuals. |
| format |
article |
| author |
Alex M. Dickens Seung Wan Yoo Alfred C. Chin Jiadi Xu Tory P. Johnson Amanda L. Trout Kurt F. Hauser Norman J. Haughey |
| author_facet |
Alex M. Dickens Seung Wan Yoo Alfred C. Chin Jiadi Xu Tory P. Johnson Amanda L. Trout Kurt F. Hauser Norman J. Haughey |
| author_sort |
Alex M. Dickens |
| title |
Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging |
| title_short |
Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging |
| title_full |
Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging |
| title_fullStr |
Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging |
| title_full_unstemmed |
Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging |
| title_sort |
chronic low-level expression of hiv-1 tat promotes a neurodegenerative phenotype with aging |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/a9afe25e6dc247338322f014d0f67320 |
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