|Department Affiliations||Comparative Medicine, Pathology, Molecular Microbiology and Immunology|
819 Miller Research Building
Emily McVey 2001 – 2007
HIV, the agent that causes acquired immunodeficiency (AIDS), is a lentivirus that causes persistent infection, immunosuppression with resultant opportunistic infections and chronic disease including encephalitis and pneumonia in humans. One of the important characteristics of the lentiviruses is their ability to replicate in macrophages; replication in these cells is linked to the development of neurological disease and pneumonia in infected individuals. There are several animal lentiviruses that provide excellent models in which to study the pathogenesis of lentiviral disease.
We have demonstrated that SIV replication in the brain induces the expression of chemokines, particularly MCP-1, that recruit lymphocytes and macrophages to the tissue. This influx of cells results in inflammation within the tissue, which may have both beneficial and detrimental effects. On the one hand, the inflammatory cells may include specific immune cells that can kill virus-infected cells and lower viral load. On the other hand, some of the inflammatory cells may themselves be infected, resulting in an increase in viral load. How these two scenarios play out in the tissue probably determines the outcome of infection.
We have recently identified an antibiotic that is inexpensive (patent has expired) and completely safe that suppresses replication of HIV/SIV and significantly suppresses the encephalitis and neurodegeneration associated with HIV/SIV infection. We are currently examining the mechanism by which this exciting drug functions in the CNS.
- Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M, Adams RJ, Bartizal C, Varrone J, Rabi SA, Graham DR, Tarwater PM, Mankowski JL, Clements JE. Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA. J Infect Dis. 2010 Jul 1;202(1):161-70.
- Clements JE, Gama L. Graham DR, Mankowski JL, Zink MC. A simian immunodeficiency virus macaque model of highly active antiretroviral treatment: viral latency in the periphery and the central nervous system. Current Opinion in HIV and AIDS 2011;6(1):37-42. PMID: 21242892
- Graham DR, Gama L, Queen SE, Li M, Brice AK, Kelly DM, Mankowski JL, Clements JE, Zink MC. Initiation of HAART during acute simian immunodeficiency virus infection rapidly controls virus replication in the CNS by enhancing immune activity and preserving protective immune responses. J Neurovirol. 2011;17(1):120-30. PMID: 21165785
- Bulterys PL, Chao A, Dalai SC, Zink MC, Dushimimana A, Katzenstein D, Saah AJ, Bulterys M. Placental malaria and mother-to-child transmission of human immunodeficiency virus-1 in rural Rwanda. Amer J of Trop Med Hyg 2011;85:202-206. PMID: 21813835
- Weed M, Adams RJ, Hienz RD, Meulendyke KA, Linde ME, Clements JE, Mankowski JL, Zink MC. SIV/macaque model of HIV infection in cocaine users: Minimal effects of cocaine on Behavior, virus replication and CNS inflammation. J Neuroimmune Pharmacol 2011 (in press). PMID: 21626125
- Meulendyke KA, Pletnikov, MV, Engle EL, Tarwater PM, Graham DR, Zink MC. Early minocycline treatment prevents a decrease in striatal dopamine in an SIV model of HIV-associated neurological disease. J Neuroimmune Pharmacol 2011 (in press).