TY - JOUR
T1 - Immune response to the West Nile virus in aged non- human primates
AU - Wertheimer, Anne M.
AU - Uhrlaub, Jennifer L.
AU - Hirsch, Alec
AU - Medigeshi, Guruprasad
AU - Sprague, Jerald
AU - Legasse, Alfred
AU - Wilk, Jennifer
AU - Wiley, Clayton A.
AU - Didier, Peter
AU - Tesh, Robert B.
AU - Murray, Kristy O.
AU - Axthelm, Michael K.
AU - Wong, Scott W.
AU - Nikolich-Žugich, Janko
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0015514
DO - 10.1371/journal.pone.0015514
M3 - Article
C2 - 21151986
AN - SCOPUS:78649943671
SN - 1932-6203
VL - 5
JO - PloS one
JF - PloS one
IS - 12
M1 - e15514
ER -