title: Tropism of dengue virus in mice and humans defined by viral nonstructural protein 3-specific immunostaining.
abstract: Previous attempts to define dengue virus (DENV) tropism in human autopsy tissues have detected DENV antigens that are abundant in circulation during severe dengue, and thus may be present in uninfected cells. To better define DENV tropism, we performed immunostaining for the DENV2 nonstructural protein 3 (NS3) in humans and in a mouse model of DENV infection. In mice, NS3 was detected in phagocytes of the spleen and lymph node, hepatocytes in liver, and myeloid cells in bone marrow. In human autopsy tissues, NS3 was present in phagocytes in lymph node and spleen, alveolar macrophages in lung, and perivascular cells in brain. This protein was also found in hepatocytes in liver and endothelial cells in spleen, although NS3 was not present in endothelium in any other tissue. Thus, NS3-specific immunostaining supports roles for infected phagocytes, hepatocytes, and, to a limited degree, endothelial cells in the pathogenesis of severe dengue.
authors.affiliation: Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley 94720-7354, California, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Balsitis
authors.forename: Josefina
authors.initials: J
authors.lastname: Coloma
authors.forename: Glenda
authors.initials: G
authors.lastname: Castro
authors.forename: Aracely
authors.initials: A
authors.lastname: Alava
authors.forename: Diana
authors.initials: D
authors.lastname: Flores
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
authors.forename: P Robert
authors.initials: PR
authors.lastname: Beatty
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D002675:Child, Preschool; D003715:Dengue / Q000821:virology*; D003716:Dengue Virus / Q000145:classification / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010586:Phagocytes / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000821:virology; D013194:Staining and Labeling; D018523:Tropism; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D017361:Viral Nonstructural Proteins