title: Case report: T-cell responses during clearance of Andes virus from blood cells 2 months after severe hantavirus cardiopulmonary syndrome.
abstract: Hantavirus Cardiopulmonary Syndrome (HCPS) due to Andes virus (ANDV) is endemic in Chile and Argentina and currently demonstrates a case-fatality rate of 37% in humans. By contrast to the chronically infected rodents, it is believed that ANDV in humans is cleared during the acute phase. Moreover, to date, both magnitude and quality of human T-cell responses during ANDV infection and clearance are unknown. Using IFN-gamma and granzyme B ELISPOT assays as well as flow cytometry, we prospectively studied the ANDV-specific T-cell responses in a 56-year-old convalescing survivor of severe HCPS, whose blood cells remained PCR-positive for ANDV-RNA until day 53 after hospital admission, that is, 67 days after infection and 42 days after discharge. PCR-negativity was closely related to the increase and function of (Gn(46-60))-specific IFN-gamma(+) granzyme B(+) CD8(+) T-cells, but not to neutralizing antibody titers. Concurrently, the phenotype of CD45RA(+)CCR7(-) Gn(46-60)-specific T-cells shifted from a CD28(-)CD27(+) "intermediate" to a CD28(-) CD27(-) "late" effector memory beyond day 53 after hospital admission. This is the first report that shows that ANDV can persist in the human hosts for more than 2 months. Moreover, the kinetics of T-cell responses during ANDV clearance may indicate a major role of T-cells for clearance of ANDV and human immunity to this pathogen.
authors.affiliation: Facultad de Medicina, Instituto de Ciencias, Clínica Alemana Universidad del Desarrollo, Santiago, Chile. tmanigold@gmail.com
authors.forename: Tobias
authors.initials: T
authors.lastname: Manigold
authors.forename: Jessica
authors.initials: J
authors.lastname: Martinez
authors.forename: Ximena
authors.initials: X
authors.lastname: Lazcano
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ye
authors.forename: Shaina
authors.initials: S
authors.lastname: Schwartz
authors.forename: Analía
authors.initials: A
authors.lastname: Cuiza
authors.forename: Francisca
authors.initials: F
authors.lastname: Valdivieso
authors.forename: Brian
authors.initials: B
authors.lastname: Hjelle
authors.forename: Pablo
authors.initials: P
authors.lastname: Vial
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002677:Chile; D053804:Granzymes / Q000378:metabolism; D006476:Orthohantavirus / Q000276:immunology*; D018804:Hantavirus Pulmonary Syndrome / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008875:Middle Aged; D009500:Neutralization Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral; D007371:Interferon-gamma; D053804:Granzymes