IMMUNE FUNCTION AND BIODEFENSE IN CHILDREN, ELDERLY, AND THE IMMUNOCOMPROMISED

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are using West Nile virus infection of aged rhesus monkeys as a model for immune function in the elderly Our collaborators at ONPRC have used aged and adult rhesus monkeys (9 total) that were implanted with telemetry devices which continuously monitored both activity and temperature at 5 minute intervals and experimentally infected them with wild type West Nile Virus (strain NY-99) These devices were implanted 7-14 days prior to infection and were removed 64 days post infection for the first cohort and 128 days post infection for the second cohort. Normal circadian cycles were recorded and although a fever was detected in one animal (20437) she was experiencing complications directly attributable to a spontaneous abortion. The other indication of infection was a slight monocytosis (measured during CBC analysis) detected in the second cohort which resolved by day 14. None of the animals displayed significant alterations in behaviors recorded twice daily by their handlers. Quantitative PCR (qPCR) was used to detect West Nile viral genomes and found that although an initial level was detectable, the virus is cleared from the blood by d100 after subcutaneous infection of 1 x 10(7)pfu/animal. Moreover, we were not able to culture infectious virus from any of the materials collected from these animals, even when qPCR indicated the presence of mRNA (not shown). In the second group, following i.v. and s.c. infection with 1 x 10(9)pfu/animal the virus was cleared by d10 . As an additional measure, we tested urine from the macaques to evaluate the possibility of viral shedding. In the group of animals given sub Q infection of 1 x 10(7) pfu/animal, our qPCR data using urine (collected via pan catch or sterile cystocentesis if possible) revealed viral genomes starting at d10 which continued until d100 whereas after i.v. + s.c. infection of 1 x 10(9) pfu/animal, virus was never detected in the urine . As mentioned, co-culture of any of the materials, including urine where viral RNA was detected, did not produce any indication of infectious virus. The animals from both cohorts successfully developed IgG responses which have peaked and are now decaying. Based on our analysis of both their blood and urine we believe the animals to be free from West Nile virus 100 post infection. Age did not affect clinical disease or viral shedding.