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

Anne M. Wertheimer, Jennifer L. Uhrlaub, Alec Hirsch, Guruprasad Medigeshi, Jerald Sprague, Alfred Legasse, Jennifer Wilk, Clayton A. Wiley, Peter Didier, Robert B. Tesh, Kristy O. Murray, Michael Axthelm, Scott Wong, Janko Nikolich-Žugich

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere15514
JournalPLoS One
Volume5
Issue number12
DOIs
StatePublished - 2010

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West Nile virus
Viruses
Primates
immune response
Macaca
Virus Diseases
Animals
T-cells
salivary glands
Culicidae
infection
Animal Models
T-lymphocytes
animal models
T-Lymphocytes
Macaca fascicularis
Viremia
viremia
extracts
Adaptive Immunity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wertheimer, A. M., Uhrlaub, J. L., Hirsch, A., Medigeshi, G., Sprague, J., Legasse, A., ... Nikolich-Žugich, J. (2010). Immune response to the West Nile virus in aged non- human primates. PLoS One, 5(12), [e15514]. https://doi.org/10.1371/journal.pone.0015514

Immune response to the West Nile virus in aged non- human primates. / Wertheimer, Anne M.; Uhrlaub, Jennifer L.; Hirsch, Alec; Medigeshi, Guruprasad; Sprague, Jerald; Legasse, Alfred; Wilk, Jennifer; Wiley, Clayton A.; Didier, Peter; Tesh, Robert B.; Murray, Kristy O.; Axthelm, Michael; Wong, Scott; Nikolich-Žugich, Janko.

In: PLoS One, Vol. 5, No. 12, e15514, 2010.

Research output: Contribution to journalArticle

Wertheimer, AM, Uhrlaub, JL, Hirsch, A, Medigeshi, G, Sprague, J, Legasse, A, Wilk, J, Wiley, CA, Didier, P, Tesh, RB, Murray, KO, Axthelm, M, Wong, S & Nikolich-Žugich, J 2010, 'Immune response to the West Nile virus in aged non- human primates', PLoS One, vol. 5, no. 12, e15514. https://doi.org/10.1371/journal.pone.0015514
Wertheimer AM, Uhrlaub JL, Hirsch A, Medigeshi G, Sprague J, Legasse A et al. Immune response to the West Nile virus in aged non- human primates. PLoS One. 2010;5(12). e15514. https://doi.org/10.1371/journal.pone.0015514
Wertheimer, Anne M. ; Uhrlaub, Jennifer L. ; Hirsch, Alec ; Medigeshi, Guruprasad ; Sprague, Jerald ; Legasse, Alfred ; Wilk, Jennifer ; Wiley, Clayton A. ; Didier, Peter ; Tesh, Robert B. ; Murray, Kristy O. ; Axthelm, Michael ; Wong, Scott ; Nikolich-Žugich, Janko. / Immune response to the West Nile virus in aged non- human primates. In: PLoS One. 2010 ; Vol. 5, No. 12.
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