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HIV integration and the establishment of latency in CCL19-treated resting CD4+ T cells require activation of NF-κB

Overview of attention for article published in Retrovirology, July 2016
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3 tweeters

Citations

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15 Dimensions

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45 Mendeley
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2 CiteULike
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Title
HIV integration and the establishment of latency in CCL19-treated resting CD4+ T cells require activation of NF-κB
Published in
Retrovirology, July 2016
DOI 10.1186/s12977-016-0284-7
Pubmed ID
Authors

Suha Saleh, Hao K. Lu, Vanessa Evans, David Harisson, Jingling Zhou, Anthony Jaworowski, Georgina Sallmann, Karey Y. Cheong, Talia M. Mota, Surekha Tennakoon, Thomas A. Angelovich, Jenny Anderson, Andrew Harman, Anthony Cunningham, Lachlan Gray, Melissa Churchill, Johnson Mak, Heidi Drummer, Dimitrios N. Vatakis, Sharon R. Lewin, Paul U. Cameron

Abstract

Eradication of HIV cannot be achieved with combination antiretroviral therapy (cART) because of the persistence of long-lived latently infected resting memory CD4(+) T cells. We previously reported that HIV latency could be established in resting CD4(+) T cells in the presence of the chemokine CCL19. To define how CCL19 facilitated the establishment of latent HIV infection, the role of chemokine receptor signalling was explored. In resting CD4(+) T cells, CCL19 induced phosphorylation of RAC-alpha serine/threonine-protein kinase (Akt), nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinase (ERK) and p38. Inhibition of the phosphoinositol-3-kinase (PI3K) and Ras/Raf/Mitogen-activated protein kinase/ERK kinase (MEK)/ERK signalling pathways inhibited HIV integration, without significant reduction in HIV nuclear entry (measured by Alu-LTR and 2-LTR circle qPCR respectively). Inhibiting activation of MEK1/ERK1/2, c-Jun N-terminal kinase (JNK), activating protein-1 (AP-1) and NF-κB, but not p38, also inhibited HIV integration. We also show that HIV integrases interact with Pin1 in CCL19-treated CD4(+) T cells and inhibition of JNK markedly reduced this interaction, suggesting that CCL19 treatment provided sufficient signals to protect HIV integrase from degradation via the proteasome pathway. Infection of CCL19-treated resting CD4(+) T cells with mutant strains of HIV, lacking NF-κB binding sites in the HIV long terminal repeat (LTR) compared to infection with wild type virus, led to a significant reduction in integration by up to 40-fold (range 1-115.4, p = 0.03). This was in contrast to only a modest reduction of 5-fold (range 1.7-11, p > 0.05) in fully activated CD4(+) T cells infected with the same mutants. Finally, we demonstrated significant differences in integration sites following HIV infection of unactivated, CCL19-treated, and fully activated CD4(+) T cells. HIV integration in CCL19-treated resting CD4(+) T cells depends on NF-κB signalling and increases the stability of HIV integrase, which allow subsequent integration and establishment of latency. These findings have implications for strategies needed to prevent the establishment, and potentially reverse, latent infection.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 2%
Ethiopia 1 2%
Unknown 43 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 24%
Student > Bachelor 6 13%
Researcher 6 13%
Other 3 7%
Student > Postgraduate 3 7%
Other 10 22%
Unknown 6 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 38%
Medicine and Dentistry 8 18%
Agricultural and Biological Sciences 5 11%
Immunology and Microbiology 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 1 2%
Unknown 7 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 August 2016.
All research outputs
#7,923,166
of 13,756,411 outputs
Outputs from Retrovirology
#464
of 805 outputs
Outputs of similar age
#123,900
of 263,379 outputs
Outputs of similar age from Retrovirology
#2
of 2 outputs
Altmetric has tracked 13,756,411 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 805 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 39th percentile – i.e., 39% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,379 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one.