The flavivirus dengue induces hypertrophy of white matter astrocytes.
Flaviviruses, including Zika and dengue (DENV), pose a serious global threat to human health. Of the 50+ million humans infected with DENV annually, approximately 1-3 % progress to severe disease manifestations, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Several factors are suspected to mediate the course of infection and pathogenesis of DENV infection. DHF and DSS are associated with vascular leakage and neurological sequelae. Our hypothesis was that altered astrocyte activation and morphology would alter the dynamics of the extracellular space and hence, neuronal and vascular function. We investigated the mechanisms of neuropathogenesis DENV infection in rhesus macaques. There were decreased numbers of GFAP immunopositive astrocytes per unit area, although those that remained had increased arbor length and complexity. This was combined with structural hypertrophy of white matter astrocytes in the absence of increased vascular leakage. Combined, these studies show how even low-grade infection with DENV induces measurable changes within the parenchyma of infected individuals.
Program in Biomedical Science, Tulane Medical School, New Orleans, LA, USA.|Tulane National Primate Research Center, Covington, LA, USA.
Kim M
KM
Lee
Tulane National Primate Research Center, Covington, LA, USA.|Department of Biomedical Engineering, Covington, LA, USA.
Kevin B
KB
Chiu
Tulane National Primate Research Center, Covington, LA, USA.
Hope A
HA
Sansing
Tulane National Primate Research Center, Covington, LA, USA.
Peter J
PJ
Didier
Program in Biomedical Science, Tulane Medical School, New Orleans, LA, USA.|Tulane National Primate Research Center, Covington, LA, USA.|Department of Microbiology and Immunology, Tulane Medical School, New Orleans, LA, USA.
Andrew A
AA
Lackner
Program in Biomedical Science, Tulane Medical School, New Orleans, LA, USA. amaclean@tulane.edu.|Tulane National Primate Research Center, Covington, LA, USA. amaclean@tulane.edu.|Department of Microbiology and Immunology, Tulane Medical School, New Orleans, LA, USA. amaclean@tulane.edu.
Andrew G
AG
MacLean
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D003715:Dengue / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D004195:Disease Models, Animal; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy; D008253:Macaca mulatta; D065288:Serogroup; D066127:White Matter / Q000378:metabolism / Q000473:pathology*; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D062826:Zonula Occludens-1 Protein
Astrocyte; Flavivirus; Glia; Hypertrophy; Neuropathogenesis