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Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment

Overview of attention for article published in Journal of Neuroinflammation, March 2017
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  • Above-average Attention Score compared to outputs of the same age (51st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (58th percentile)

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Title
Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment
Published in
Journal of Neuroinflammation, March 2017
DOI 10.1186/s12974-017-0848-z
Pubmed ID
Authors

Sanjay R. Mehta, Josué Pérez-Santiago, Todd Hulgan, Tyler R. C. Day, Jill Barnholtz-Sloan, Haley Gittleman, Scott Letendre, Ronald Ellis, Robert Heaton, Stephanie Patton, Jesse D. Suben, Donald Franklin, Debralee Rosario, David B. Clifford, Ann C. Collier, Christina M. Marra, Benjamin B. Gelman, Justin McArthur, Allen McCutchan, Susan Morgello, David Simpson, James Connor, Igor Grant, Asha Kallianpur

Abstract

Mitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. We quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS < 0.5, unimpaired). CSF, clinical, and biomarker data from the earliest available time point were analyzed. Cell-free mtDNA associations with CSF inflammation and iron-related biomarkers [CXCL10, IL-6, IL-8, TNF-a, transferrin (TF), ceruloplasmin (CP), and vascular endothelial growth factor (VEGF)], VL, and GDS were evaluated by multivariable regression. CSF cell-free mtDNA levels were significantly lower in participants with undetectable (vs. detectable) VL in either plasma (p < 0.001) or CSF (p < 0.001) and in those on antiretroviral therapy (ART; p < 0.001). Participants on ART with undetectable VL in both CSF and plasma had lower mtDNA levels than those with detectable VL in both compartments (p = 0.001). Higher mtDNA levels were observed in participants in the highest vs. lowest tertile (T3 vs. T1) of CSF CXCL10 (T3 vs. T1, p < 0.001) and TNF-a (T3 vs. T1, p < 0.05) in unadjusted analyses. MtDNA levels also correlated with CSF leukocyte count. After adjusting for CSF leukocyte count and VL, mtDNA levels were also associated with other inflammation- and iron-related biomarkers in CSF, including TF (T3 vs. T1, p < 0.05) and CP (T3 vs. T1, p < 0.05). With additional correction for ART use, mtDNA was also negatively associated with CSF VEGF (p < 0.05) and IL-6 (p = 0.05). We observed no associations of CSF mtDNA levels with age or GDS-defined NC impairment. CSF cell-free mtDNA levels were associated with HIV RNA and ART status, as well as with biomarkers of iron transport and VEGF, a growth factor with known effects on mitochondrial integrity and autophagy. CSF mtDNA may be a biomarker of iron dysregulation and/or neuroinflammation during HIV infection.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 84 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 84 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 15%
Student > Master 11 13%
Student > Bachelor 10 12%
Researcher 7 8%
Professor 5 6%
Other 12 14%
Unknown 26 31%
Readers by discipline Count As %
Medicine and Dentistry 15 18%
Agricultural and Biological Sciences 9 11%
Nursing and Health Professions 6 7%
Biochemistry, Genetics and Molecular Biology 5 6%
Neuroscience 5 6%
Other 11 13%
Unknown 33 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 06 April 2017.
All research outputs
#12,972,426
of 22,962,258 outputs
Outputs from Journal of Neuroinflammation
#1,367
of 2,649 outputs
Outputs of similar age
#148,525
of 309,402 outputs
Outputs of similar age from Journal of Neuroinflammation
#23
of 55 outputs
Altmetric has tracked 22,962,258 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,649 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 48th percentile – i.e., 48% 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 309,402 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 55 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.