title: Platelet activation and platelet-monocyte aggregate formation contribute to decreased platelet count during acute simian immunodeficiency virus infection in pig-tailed macaques.
abstract: Platelets are key participants in innate immune responses to pathogens. As a decrease in circulating platelet count is one of the initial hematologic indicators of human immunodeficiency virus (HIV) infection, we sought to determine whether decline in platelet number during acute infection results from decreased production, increased antibody-mediated destruction, or increased platelet activation in a simian immunodeficiency virus (SIV)/macaque model. During acute SIV infection, circulating platelets were activated with increased surface expression of P-selection, CD40L and major histocompatibility complex class I. Platelet production was maintained and platelet autoantibodies were not detected during acute infection. Concurrent with a decrease in platelet numbers and an increase in circulating monocytes, platelets were found sequestered in platelet-monocyte aggregates, thereby contributing to the decline in platelet counts. Because the majority of circulating CD16(+) monocytes formed complexes with platelets during acute SIV infection, a decreased platelet count may represent platelet participation in the innate immune response to HIV.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Metcalf Pate
authors.forename: Claire E
authors.initials: CE
authors.lastname: Lyons
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Dorsey
authors.forename: Erin N
authors.initials: EN
authors.lastname: Shirk
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Queen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: Lucio
authors.initials: L
authors.lastname: Gama
authors.forename: Craig N
authors.initials: CN
authors.lastname: Morrell
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology* / Q000821:virology; D023201:CD40 Ligand / Q000378:metabolism; D002449:Cell Aggregation; D004195:Disease Models, Animal; D005805:Genes, MHC Class I; D007113:Immunity, Innate; D008251:Macaca; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010976:Platelet Count; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology*; D015302:Simian Immunodeficiency Virus; D013552:Swine
chemical_list: D001323:Autoantibodies; D019007:P-Selectin; D023201:CD40 Ligand
keywords: CD16+ monocyte; HIV; SIV; macaque; platelet activation; platelet-monocyte aggregate; thrombocytopenia