Immune Response to the West Nile Virus in Aged Non-Human PrimatesReportar como inadecuado




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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 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-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.



Autor: Anne M. Wertheimer, Jennifer L. Uhrlaub, Alec Hirsch, Guruprasad Medigeshi, Jerald Sprague, Alfred Legasse, Jennifer Wilk, Clayto

Fuente: http://plos.srce.hr/



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