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Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2014 Jun; Vol. 124 (6), pp. 2802-6. Date of Electronic Publication: 2014 May 16. - Publication Year :
- 2014
-
Abstract
- Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
HIV Infections microbiology
HIV Infections therapy
Humans
Intestinal Mucosa immunology
Intestinal Mucosa pathology
Intestinal Mucosa virology
Macaca nemestrina
Sevelamer
Simian Acquired Immunodeficiency Syndrome virology
Simian Immunodeficiency Virus physiology
Viral Load drug effects
Virus Replication
Bacterial Translocation drug effects
Polyamines pharmacology
Simian Acquired Immunodeficiency Syndrome drug therapy
Simian Acquired Immunodeficiency Syndrome microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 124
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 24837437
- Full Text :
- https://doi.org/10.1172/JCI75090