title: Immune response to the West Nile virus in aged non-human primates.
abstract: BACKGROUND
  Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Understanding the basis of this susceptibility requires development of suitable animal models. Here, we investigated the immune response to WNV in old non-human primates.
  
  
  RESULTS
  We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17-30 yrs) and adult (6-9 yrs) Rhesus macaques (RM) were challenged with WNV in the presence or the absence of the mosquito salivary gland extract (SGE) to approximate natural infection. None of the 26 animals exhibited clinical signs of the disease. Quantitative PCR suggested discrete and short-lived viremia, but infectious virus was never isolated. There was markedly increased, age-independent, proliferation of CD3(-) non-B cells, followed by B-cell proliferation, which correlated to the loss of detectable WNV genomes. Moreover, animals primed with mosquito salivary gland extract exhibited reduced circulating WNV RNA. While we found the expected age-associated reduction in T cell proliferation, adaptive immunity did not correlate with infection outcome. That was further confirmed in a cohort of thymectomized and/or CD8 T-cell depleted Cynomolgus macaques (CM; N = 15), who also failed to develop WNV disease.
  
  
  CONCLUSIONS
  Results are consistent with strong and age-independent innate resistance of macaques against WNV challenge. This animal model is therefore not suitable for vaccine and therapeutic testing against WNV. However, understanding the basis of their innate resistance against WNV in macaques could provide helpful clues to improve anti-WNV protection of older adults.
authors.affiliation: Arizona Center on Aging, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Wertheimer
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Uhrlaub
authors.forename: Alec
authors.initials: A
authors.lastname: Hirsch
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Medigeshi
authors.forename: Jerald
authors.initials: J
authors.lastname: Sprague
authors.forename: Alfred
authors.initials: A
authors.lastname: Legasse
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wilk
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
authors.forename: Peter
authors.initials: P
authors.lastname: Didier
authors.forename: Robert B
authors.initials: RB
authors.lastname: Tesh
authors.forename: Kristy O
authors.initials: KO
authors.lastname: Murray
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Scott W
authors.initials: SW
authors.lastname: Wong
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Žugich
mesh_terms: D000375:Aging; D000818:Animals; D009033:Culicidae; D004195:Disease Models, Animal; D005260:Female; D016679:Genome, Viral; D007107:Immune System; D007962:Leukocytes / Q000821:virology; D008251:Macaca; D008252:Macaca fascicularis; D008297:Male; D011323:Primates; D012469:Salivary Glands / Q000821:virology; D020305:Strigiformes; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology*; D014902:West Nile virus / Q000378:metabolism*