|Department Affiliations||Department of Molecular & Comparative Pathobiology Departments of Molecular Biology & Genetics, Neurology & Pathology|
|Rank||Professor and Vice Dean for Faculty|
|SOM Address||839 Miller Research Building|
Terri Shieh-Newton 1996 – 1999
Lentiviruses, HIV being the best known, are non-oncogenic retroviruses that cause chronic progressive diseases of the immune system, central nervous system, lungs and joints. My laboratory seeks to understand the molecular basis for virus cell-interactions that lead to cell dysfunction, damage and ultimately disease in infected humans and animals. We use the simian immunodeficiency virus (SIV) as an animal model of AIDS. We have shown the importance of infection of cells by a CD4-independent pathway that is particularly important for infection of cells in the central nervous system (CNS). In primary cells derived from the brain, neurovirulent molecular clones of SIV (ones that cause CNS disease) infect cells via a CD4-independent, chemokine receptor-dependent (CCR5) pathway. Infection of the CNS is a frequent result of HIV-1 infection of humans and the SIV model provides the best model to study the contribution of viral and cellular genes in the disease process.
Recent studies in vivo and in vitro have identified the role of innate immune responses that regulate viral gene expression at the transcriptional and post-transcriptional level. IFNis induced in SIV and HIV infected cells resulting in the induction of cellular transcription factors that repress viral transcription in macrophages. The molecular mechanisms involved in the regulation of HIV and SIV is being studied in specific cells and tissues in a well defined animal model and primary cells. In addition, post-transcriptional mechanisms induced by the innate immune response also restrict virus replication and these involve the PML protein both in vitro and in vivo. Understanding these regulatory mechanisms is essential for understanding the pathogenesis of HIV induced AIDS and CNS diseases such as dementia and peripheral neuropathy.
- Barber SA, Herbst DS, Bullock BT, Gama L, Clements JE. Innate immune responses and control of acute simian immunodeficiency virus replication in the central nervous system. J Neurovirol. 2004;10 Suppl 1:15-20.
- Shen A, Zink MC, Mankowski JL, Chadwick K, Margolick JB, Carruth LM, Li M, Clements JE, Siliciano RF. Resting CD4+ T lymphocytes but not thymocytes provide a latent viral reservoir in a simian immunodeficiency virus-Macaca nemestrina model of human immunodeficiency virus type 1-infected patients on highly active antiretroviral therapy. J Virol. 2003 Apr;77(8):4938-49
- Rue SM, Roos JW, Amzel LM, Clements JE, Barber SA.Hydrogen bonding at a conserved threonine in lentivirus capsid is required for virus replication. J Virol. 2003 ;77(14):8009
- Clements, J.E., Babas, T., Mankowski, J., Suryanarayana, K., Piatak, M.J., Tarwater, P.M., Lifson, J., and Zink, M.C. The CNS is a Reservoir for SIV: Steady-state levels of SIV DNA in Brain from acute through asymptomatic infection. J. Infect. Dis. 186:905-13 2002.
- Barber, S.A., Bruett, L., and Clements, J.E. Involvement of a membrane-associated Serine/Threonine kinase complex in cellular binding of visna virus. Virology, 274:321-330, 2000.