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Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions

Overview of attention for article published in Retrovirology: Research & Treatment, June 2013
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2 tweeters

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16 Dimensions

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15 Mendeley
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Title
Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions
Published in
Retrovirology: Research & Treatment, June 2013
DOI 10.1186/1742-4690-10-59
Pubmed ID
Authors

Maria S Manoussaka, Neil Berry, Deborah Ferguson, Richard Stebbings, Mark Robinson, Claire Ham, Mark Page, Bo Li, Atze T Das, Ben Berkhout, Neil Almond, Martin P Cranage

Abstract

BACKGROUND: Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. RESULTS: Using a novel, doxycycline dependent, replication-competent live-attenuated SIVmac239Deltanef (SIV-rtTADeltanef), we show that under replication-permissive conditions SIV-rtTADeltanef is fully viable. Twelve rhesus macaques were infected with a peak plasma vRNA on average two log10 lower than in 6 macaques infected with unconditionally replication-competent SIVDeltanef. Consistent with the attenuated phenotype of the viruses the majority of animals displayed low or undetectable levels of viraemia by 42-84 days after infection. Next, comparison of circulating T cells before and after chronic infection with parental SIVDeltanef revealed a profound global polarisation toward CD28-CCR7- T-effector memory 2 (TEM2) cells within CD95+CD4+ and CD95+CD8+ populations. Critically, a similar effect was seen in the CD95+ CD4+ population and to somewhat lesser extent in the CD95+ CD8+ population of SIV-rtTADeltanef chronically infected macaques that were maintained on doxycycline, but was not seen in animals from which doxycycline had been withdrawn. The proportions of gut-homing T-central memory (TCM) and TEM defined by the expression of alpha4beta7 and CD95 and differential expression of CD28 were increased in CD4 and CD8 cells under replication competent conditions and gut-homing CD4 TCM were also significantly increased under non-permissive conditions. TEM2 polarisation was seen in the small intestines of animals under replication permissive conditions but the effect was less pronounced than in the circulation. Intracellular cytokine staining of circulating SIV-specific T cells for IL-2, IFN-gamma, TNF-alpha and IL-17 showed that the extent of polyfunctionality in CD4 and CD8 T cells was associated with replication permissivity; however, signature patterns of cytokine combinations were not distinguishable between groups of macaques. CONCLUSION: Taken together our results show that the global T memory cell compartment is profoundly skewed towards a mature effector phenotype by attenuated SIV. Results with the replication-conditional mutant suggest that maintenance of this effect, that may be important in vaccine design, might require persistence of replicating virus.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 27%
Researcher 3 20%
Other 2 13%
Student > Postgraduate 2 13%
Student > Master 2 13%
Other 1 7%
Unknown 1 7%
Readers by discipline Count As %
Immunology and Microbiology 6 40%
Medicine and Dentistry 3 20%
Agricultural and Biological Sciences 3 20%
Biochemistry, Genetics and Molecular Biology 2 13%
Unknown 1 7%

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 10 June 2013.
All research outputs
#6,407,354
of 10,677,937 outputs
Outputs from Retrovirology: Research & Treatment
#238
of 453 outputs
Outputs of similar age
#67,037
of 131,151 outputs
Outputs of similar age from Retrovirology: Research & Treatment
#14
of 25 outputs
Altmetric has tracked 10,677,937 research outputs across all sources so far. This one is in the 24th percentile – i.e., 24% of other outputs scored the same or lower than it.
So far Altmetric has tracked 453 research outputs from this source. They receive a mean Attention Score of 3.9. This one is in the 33rd percentile – i.e., 33% 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 131,151 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 25 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.