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PLoS Pathog. 2014 Dec 11;10(12):e1004533. doi: 10.1371/journal.ppat.1004533. eCollection 2014 Dec.

Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

Author information

1
Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America.
2
Department of Radiology, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Neuroscience, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
3
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, United States of America.
4
Department of Biomedical Sciences, Section of Anatomic Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
5
Department of Radiology, Harvard Medical School, Boston, Massachusetts, United States of America.

Abstract

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

PMID:
25502752
PMCID:
PMC4263764
DOI:
10.1371/journal.ppat.1004533
[Indexed for MEDLINE]
Free PMC Article

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