#126 Experimental infection of birds with West Nile virus: Level of infection in the CNS

Abstract

Clinical and epidemiological studies suggest that the host autonomic nervous system (ANS)might influenceHIVpathogenesis. To investigate the neuroanatomical basis for sympathetic nervous system (SNS) influences on lentiviral pathogenesis, we analyzed the spatial relationship between catecholaminergic neurons and SIV replication in lymph nodes from rhesus macaques experimentally infected with SIVmac251. Sites of viral replication were mapped by in situ hybridization for SIV env, gag, and nefRNA, and catecolaminergic neurons from the sympathetic nervous system were mapped by SPG chemofluorescence. Spatial statistical analyses showed that active SIV replication was 3.8-fold more likely to occur in the vicinity of catecholaminergic neurons (p < .0001). Density of both SNS innervation and SIV replication differed across cortical, paracortical, and medullary regions of the lymph node, but analyses of each region separately continued to show increased SIV replication in the vicinity of catecholaminergic neurons. Comparisons with lymph nodes fromuninfected rhesusmacaques revealed a 38% reduction in the density of SNSneurons in tissues from SIV-infected animals, suggesting that lentiviral pathogenesis might deplete lymph node neurons. Consistent with this hypothesis, the number of SIV replication sites was inversely correlated with the density of catecholaminergic neurons among SIV-infected animals. These data are consistent with human clinical studies and in vitro experimental studies in suggesting that catecholamine neurotransmitters from the SNS might enhance progression of lentiviral infection. Given the deleterious effects of SIV infection on neural density, these results also suggest that SNS influences may be most pronounced during the early phases of infection prior to virally induced depletion of lymph node neurons. Sources of support: National Institute of Mental Health (MH049033), the National Institutes of Allergy and Infectious Disease and Neurological Disorders and Stroke (AI/ NS52737), the University of California University wide AIDS Research Program (CC99-LA-02), the Norman Cousins Center for Psychoneuroimmunology, and the James B. Pendelton Charitable Trust.