HIV infection is associated with functional abnormalities of B lymphocytes, including hypergammaglobulinemia, presence of high numbers of spontaneously activated immunoglobulin-secreting cells in the circulation, and the presence of autoantibodies in serum. The steady, long term activation of B lymphocytes, which seems specific for either HIV determinants or other antigens, might play a crucial role in the pathogenesis of the immune system damage observed during the course of the HIV-induced disease. The objective of this study is the definition of AIDS-associated autoimmune phenomena in the SIV-infected rhesus macaque model. We have tested several uninfected and infected animals for the presence of anti-single stranded (ss) DNA and anti-double stranded (ds) DNA antibodies. In general, anti-ssDNA antibodies are present in a variety of autoimmune diseases and in a few normal individuals, whereas anti-dsDNA antibodies are present in 50% to 70% of patients with systemic lu pus erythematosus (SLE). First, we tested sera from 33 normal and 21 SIV-infected macaques for presence of anti-ssDNA and anti-dsDNA antibodies by ELISA. Second, we tested sera collected from three SIV-infected rhesus macaques prior and at two different time-points after infection. Both anti-ssDNA and anti-dsDNA antibodies are produced by SIV-infected rhesus macaques. The means of the samples (normal versus SIV-infected macaques) are different at the 0.05 level. In the three SIV-infected macaques, anti-DNA antibodies were present at very low level prior to infection. The titers progressively increased following infection. These data demonstrate that infection with SIV triggers the production of anti-DNA antibodies and, therefore, validate the use of SIV-infected rhesus macaques for the study of AIDS-related autoimmune phenomena. To define the mechanisms that lead to the production of these autoantibodies and to test the hypothesis that B cell superantigens are involved in these mechan isms, we are performing a series of experiments, which include the analysis of the effects that recombinant SIV antigens have on B cell activation and expression of cell-surface antigens.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
3P51RR000165-37S1
Application #
2711836
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Emory University
Department
Type
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Walker, Lary C (2018) Prion-like mechanisms in Alzheimer disease. Handb Clin Neurol 153:303-319
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Wakeford, Alison G P; Morin, Elyse L; Bramlett, Sara N et al. (2018) A review of nonhuman primate models of early life stress and adolescent drug abuse. Neurobiol Stress 9:188-198
Singh, Arun; Jenkins, Meagan A; Burke Jr, Kenneth J et al. (2018) Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates. Cell Rep 22:941-952
Maddox, S A; Kilaru, V; Shin, J et al. (2018) Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD. Mol Psychiatry 23:658-665
Li, Chun-Xia; Kempf, Doty J; Tong, Frank C et al. (2018) Longitudinal MRI Evaluation of Ischemic Stroke in the Basal Ganglia of a Rhesus Macaque (Macaca mulatta) with Seizures. Comp Med :
Lacreuse, Agnès; Parr, Lisa; Chennareddi, Lakshmi et al. (2018) Age-related decline in cognitive flexibility in female chimpanzees. Neurobiol Aging 72:83-88
Meng, Yuguang; Hu, Xiaoping; Zhang, Xiaodong et al. (2018) Diffusion tensor imaging reveals microstructural alterations in corpus callosum and associated transcallosal fiber tracts in adult macaques with neonatal hippocampal lesions. Hippocampus 28:838-845

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