Serious CNS dysfunction is the preeminent complication of HIV infections of infants and children. By elucidating the initial immunopathologic mechanisms of perinatal HIV subsequent CNS pathology. Epidemiologic data suggest that the fetus and neonate may be uniquely susceptible to HIV infections and disease progression, especially CNS dysfunction. As only a relatively small proportion of lymphocytes from HIV infected individuals show the presence of virus, disease progression may also be due to noninfectious effects of HIV-derived soluble products on the immune system. We have shown that the envelope proteins of HIV are immunoregulatory and can suppress the immune functions of the infected host. This project will assess lymphocyte responses of the fetus and neonate to a panel of recombinant and synthetic HIV-specific peptides. By comparing responses of adult donor lymphocytes we may identify mechanisms which render the fetus or neonate uniquely susceptible to HIV infection, CNS dysfunction and the immunosuppressive effects of HIV peptides. We shall utilize a defined in vitro model system consisting of cord blood or adult peripheral lymphocytes pretreated with recombinant and synthetic HIV peptides and subsequently examined for various functional activities. Cord blood donors will be stratified into mothers at high and low risk of HIV infection. We shall also attempt to stratify our data on the basis of the ethnicity or race of the cord blood donors to see if immunologic function may be associated with this variable. The high risk cohort will be further divided into HIV+ and HIV- groups. The responses of cord lymphocytes to HIV peptides will be compared to lymphocyte responses from healthy adult donors and possibly children from different age groups. Lymphocytes preincubated with HIV peptides will be then treated in vitro with several biological modifier substances to identify potential agents capable of reversing the adverse effects of HIV peptides. These studies may define unique immunologic properties of the perinatal period which increase the susceptibility of the fetus or neonate to HIV infection and progression to the CNS consequences of pediatric AIDS. The identification of agents useful in the prophylaxis of the high-risk fetus against HIV infections and/or disease progression involving the CNS could be derived from this project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH047225-01
Application #
3387028
Study Section
MH Acquired Immunodeficiency Syndrome Research Review Committee (MHAZ)
Project Start
1990-08-01
Project End
1995-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Ludwig, Linda B; Ambrus Jr, Julian L; Krawczyk, Kristie A et al. (2006) Human Immunodeficiency Virus-Type 1 LTR DNA contains an intrinsic gene producing antisense RNA and protein products. Retrovirology 3:80
Nair, Narayanan; Mahajan, Supriya; Chawda, Ram et al. (2002) Grape seed extract activates Th1 cells in vitro. Clin Diagn Lab Immunol 9:470-6
Nair, Madhavan P; Kandaswami, Chithan; Mahajan, Supriya et al. (2002) Grape seed extract proanthocyanidins downregulate HIV-1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells. Biol Res 35:421-31
Nair, Madhavan P N; Kandaswami, Chithan; Mahajan, Supriya et al. (2002) The flavonoid, quercetin, differentially regulates Th-1 (IFNgamma) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells. Biochim Biophys Acta 1593:29-36
Nair, M P; Mahajan, S; Chadha, K C et al. (2001) Effect of cocaine on chemokine and CCR-5 gene expression by mononuclear cells from normal donors and HIV-1 infected patients. Adv Exp Med Biol 493:235-40
Schwartz, S A (2000) Intravenous immunoglobulin treatment of immunodeficiency disorders. Pediatr Clin North Am 47:1355-69
Nair MPN; Mahajan, S; Hou, J et al. (2000) The stress hormone, cortisol, synergizes with HIV-1 gp-120 to induce apoptosis of normal human peripheral blood mononuclear cells. Cell Mol Biol (Noisy-le-grand) 46:1227-38
Schwartz, S A; Nair, M P (1999) Current concepts in human immunodeficiency virus infection and AIDS. Clin Diagn Lab Immunol 6:295-305
Nair, M P; Schwartz, S A; Polasani, R et al. (1997) Immunoregulatory effects of morphine on human lymphocytes. Clin Diagn Lab Immunol 4:127-32
Schwartz, S A; Nair, M P (1997) Molecular mechanisms in the pathogenesis of AIDS encephalopathy. Cell Mol Biol (Noisy-le-grand) 43:925-33

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