Professor & Director, Department of Molecular and Comparative Pathobiology
Professor, Department of Pathology &
Department of Molecular Microbiology and Immunology
at Bloomberg School of Public Health
733 N. Broadway, BRB 819
410-955-9770
410-955-9823 (Fax)
mczink@jhmi.edu
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.
Recent Publications
Barber SA, Uhrlaub JL, DeWitt JB, Tarwater PM, Zink MC. Dysregulation of mitogen-activated protein kinase (MAPK) signaling pathways in SIV encephalitis. Am J Pathol 2004;164:355-362.
Zink MC, Uhrlaub J, DeWitt JB, Voelker T, Bullock BT, Mankowski JL, Tarwater PM, Clements JE, Barber SA. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. J. American Medical Assoc. 2005;293:2003-2011.
Overholser ED, Babas T, Zink MC, Barber SA, Clements JE. CD4-Independent entry and replication of simian immunodeficiency virus in primary rhesus macaque astrocytes are regulated by the transmembrane protein. J Virol 2005;8:4944-4951.
Babas T, DeWitt JB, Mankowski JL, Tarwater PM, Clements JE, Zink MC. Ongoing selection for neurovirulent genotypes in the brain of simian immunodeficiency virus (SIV) infected macaques from acute through terminal infection. AIDS 2006;9:197-205
Barber SA, Gama L, Li M, Voelker T, Anderson JE, Zink MC, Tarwater PM, Carruth LM, Clements JE.Longitudinal Analysis of Simian Immunodeficiency Virus (SIV) Replication in the Lungs: Compartmentalized Regulation of SIV. J Infect Dis. 2006 Oct 1;194(7):931-8.
Zink MC, Laast VA, Helke KL, Brice AK, Barber SA, Clements JE, Mankowski JL. From Mice to Macaques – Animal Models of HIV Nervous System Disease. Curr HIV Res. 2006 Jul;4(3):293-305
