title: Multivariate statistical analyses demonstrate unique host immune responses to single and dual lentiviral infection.
abstract: BACKGROUND
  Feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) are recently identified lentiviruses that cause progressive immune decline and ultimately death in infected cats and humans. It is of great interest to understand how to prevent immune system collapse caused by these lentiviruses. We recently described that disease caused by a virulent FIV strain in cats can be attenuated if animals are first infected with a feline immunodeficiency virus derived from a wild cougar. The detailed temporal tracking of cat immunological parameters in response to two viral infections resulted in high-dimensional datasets containing variables that exhibit strong co-variation. Initial analyses of these complex data using univariate statistical techniques did not account for interactions among immunological response variables and therefore potentially obscured significant effects between infection state and immunological parameters.
  
  
  RESULTS
  Here, we apply a suite of multivariate statistical tools, including Principal Component Analysis, MANOVA and Linear Discriminant Analysis, to temporal immunological data resulting from FIV superinfection in domestic cats. We investigated the co-variation among immunological responses, the differences in immune parameters among four groups of five cats each (uninfected, single and dual infected animals), and the "immune profiles" that discriminate among them over the first four weeks following superinfection. Dual infected cats mount an immune response by 24 days post superinfection that is characterized by elevated levels of CD8 and CD25 cells and increased expression of IL4 and IFNgamma, and FAS. This profile discriminates dual infected cats from cats infected with FIV alone, which show high IL-10 and lower numbers of CD8 and CD25 cells.
  
  
  CONCLUSIONS
  Multivariate statistical analyses demonstrate both the dynamic nature of the immune response to FIV single and dual infection and the development of a unique immunological profile in dual infected cats, which are protected from immune decline.
authors.affiliation: Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Sunando
authors.initials: S
authors.lastname: Roy
authors.forename: Jennie
authors.initials: J
authors.lastname: Lavine
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiaromonte
authors.forename: Julie
authors.initials: J
authors.lastname: Terwee
authors.forename: Sue
authors.initials: S
authors.lastname: VandeWoude
authors.forename: Ottar
authors.initials: O
authors.lastname: Bjornstad
authors.forename: Mary
authors.initials: M
authors.lastname: Poss
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000096:biosynthesis; D002415:Cats; D003627:Data Interpretation, Statistical; D016181:Feline Acquired Immunodeficiency Syndrome / Q000378:metabolism; D016089:Immunodeficiency Virus, Feline / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D016086:Lentivirus / Q000378:metabolism*; D015233:Models, Statistical; D015999:Multivariate Analysis; D025341:Principal Component Analysis
chemical_list: D016827:CD8 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma