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Viral Load, Telomere Length and Microbial Communities in the Gut Lung Axis of HIV Donors
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A6090 - Viral Load, Telomere Length and Microbial Communities in the Gut Lung Axis of HIV Donors
Author Block: J. Yang, D. A. Ngan, S. Tam, J. Leung, D. D. Sin, S. P. Man; Centre for Heart Lung Innovation, Vancouver, BC, Canada.
RATIONALE: Previous studies have demonstrated the existence of a gut-lung axis and its proposed role in altering immune response and respiratory disease pathogenesis. The lung and gut microbiome has been individually studied in the context of Human Immunodeficiency Virus (HIV) infection, however the gut-lung axis in HIV remains relatively unexplored and requires further investigation. Whether alterations in the gut-lung axis contribute to the propensity towards age-related diseases observed in HIV is unclear. This study examined the microbiomes of the gut-lung axis and measures of cellular senescence in HIV subjects using paired human lung and small intestine tissue.
METHODS: Paired lung and small intestine tissue autopsy specimens were obtained from HIV-positive and HIV-negative donors through the National NeuroAIDS Tissue Consortium (NNTC). Frozen samples were sectioned on dry ice and weighed for DNA extraction using the QIAGEN DNeasy® Blood and Tissue kit. Quantitative PCR was performed to determine absolute telomere length (aTL) by using telomere and 36B4 standards. The 16S rRNA V4 region was sequenced using the MiSeq sequencing platform. Extraction negatives were run through the entire workflow alongside samples for quality control. Raw sequence reads were processed using Mothur (v.1.39.5) followed by statistical analysis using R studio. Student’s t-test, PERMANOVA and ANCOVA were used for statistical analysis.
RESULTS: In HIV-positive donors, HIV viral load (copies/mL) was positively associated with aTL in lung tissue after age-adjustment (R2=0.38, p=0.031). There was no association between viral load and aTL in the small intestine. In HIV-negative patients, aTL in the small intestine appeared to stay relatively stable across age groups, distinct from HIV-positive patients in whom aTL displayed a trend of shortening with age (difference in slopes, p=0.055). In contrast, in the lung, HIV had no effect on the relationship between aTL with age. There were no significant differences in overall microbial community composition between HIV-positive and HIV-negative donors in lung and small intestinal samples. The three most prominent phyla in HIV-positive and HIV-negative donors were Bacteroidetes, Firmicutes and Proteobacteria in both lung and small intestine. HIV-positive donors had a trend towards lower Actinobacteria in the lung (p=0.060) compared to HIV-negative donors, but this trend is not evident in the small intestine.
CONCLUSION: Viral load is associated with telomere length in lung but not gut tissue. These data suggest that viral infection in HIV plays a role in lung tissue aging and may contribute to the pathogenesis of early emphysema in HIV.
Author Block: J. Yang, D. A. Ngan, S. Tam, J. Leung, D. D. Sin, S. P. Man; Centre for Heart Lung Innovation, Vancouver, BC, Canada.
RATIONALE: Previous studies have demonstrated the existence of a gut-lung axis and its proposed role in altering immune response and respiratory disease pathogenesis. The lung and gut microbiome has been individually studied in the context of Human Immunodeficiency Virus (HIV) infection, however the gut-lung axis in HIV remains relatively unexplored and requires further investigation. Whether alterations in the gut-lung axis contribute to the propensity towards age-related diseases observed in HIV is unclear. This study examined the microbiomes of the gut-lung axis and measures of cellular senescence in HIV subjects using paired human lung and small intestine tissue.
METHODS: Paired lung and small intestine tissue autopsy specimens were obtained from HIV-positive and HIV-negative donors through the National NeuroAIDS Tissue Consortium (NNTC). Frozen samples were sectioned on dry ice and weighed for DNA extraction using the QIAGEN DNeasy® Blood and Tissue kit. Quantitative PCR was performed to determine absolute telomere length (aTL) by using telomere and 36B4 standards. The 16S rRNA V4 region was sequenced using the MiSeq sequencing platform. Extraction negatives were run through the entire workflow alongside samples for quality control. Raw sequence reads were processed using Mothur (v.1.39.5) followed by statistical analysis using R studio. Student’s t-test, PERMANOVA and ANCOVA were used for statistical analysis.
RESULTS: In HIV-positive donors, HIV viral load (copies/mL) was positively associated with aTL in lung tissue after age-adjustment (R2=0.38, p=0.031). There was no association between viral load and aTL in the small intestine. In HIV-negative patients, aTL in the small intestine appeared to stay relatively stable across age groups, distinct from HIV-positive patients in whom aTL displayed a trend of shortening with age (difference in slopes, p=0.055). In contrast, in the lung, HIV had no effect on the relationship between aTL with age. There were no significant differences in overall microbial community composition between HIV-positive and HIV-negative donors in lung and small intestinal samples. The three most prominent phyla in HIV-positive and HIV-negative donors were Bacteroidetes, Firmicutes and Proteobacteria in both lung and small intestine. HIV-positive donors had a trend towards lower Actinobacteria in the lung (p=0.060) compared to HIV-negative donors, but this trend is not evident in the small intestine.
CONCLUSION: Viral load is associated with telomere length in lung but not gut tissue. These data suggest that viral infection in HIV plays a role in lung tissue aging and may contribute to the pathogenesis of early emphysema in HIV.
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