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Immune response to the West Nile virus in aged non- human primates

Wertheimer, AM and Uhrlaub, JL and Hirsch, A and Medigeshi, G and Sprague, J and Legasse, A and Wilk, J and Wiley, CA and Didier, P and Tesh, RB and Murray, KO and Axthelm, MK and Wong, SW and Nikolich-Žugich, J (2010) Immune response to the West Nile virus in aged non- human primates. PLoS ONE, 5 (12).

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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. Methodology/Principal Findings: We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17-30yrs) and adult (6-9yrs) 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 Bcell 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/significance: 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. © 2010 Wertheimer et al. -


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wertheimer, AM
Uhrlaub, JL
Hirsch, A
Medigeshi, G
Sprague, J
Legasse, A
Wilk, J
Wiley, CAwiley1@pitt.eduWILEY1
Didier, P
Tesh, RB
Murray, KO
Axthelm, MK
Wong, SW
Nikolich-Žugich, J
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorFooks, Anthony R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 15 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0015514
Refereed: Yes
MeSH Headings: Aging; Animals; Culicidae; Disease Models, Animal; Female; Genome, Viral; Immune System; Leukocytes--virology; Macaca; Macaca fascicularis; Male; Primates; Salivary Glands--virology; Strigiformes; West Nile Fever--immunology; West Nile Fever--virology; West Nile virus--metabolism
Other ID: NLM PMC2996299
PubMed Central ID: PMC2996299
PubMed ID: 21151986
Date Deposited: 22 Aug 2012 21:53
Last Modified: 30 Mar 2021 14:56
URI: http://d-scholarship.pitt.edu/id/eprint/13578

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