Daniel Kronemann

E-mail: kron0089@umn.edu

Thesis Advisor: Wade Bresnahan

Year entered: 2004

Degrees received:
B.S., Microbiology/Biochemistry, University of Idaho, Moscow, ID 2002

Thesis research:
In tissue culture, HIV-1 rapidly infects and kills CD4+ cells.  This is consistent with a decline in the CD4+ T cell population in the host, which is a hallmark of HIV-1 disease progression.  However, in a human host, viral replication is partially controlled by mounting an immune response.  Innate and adaptive immune responses reduce the amount of virus produced by reducing viral production and populations of productively infected cells.  The antigen is never cleared in HIV-1 infection and results in a chronic exposure pro-inflammatory cytokines and immune activation which promotes viral replication and immune suppression.  The host uses moderators of inflammation in an attempt to control the chronic immune activation.  Ultimately, the balance of the effects of chronic immune activation and inflammation, and the attempts to moderate the immune activation and inflammation, shifts in favor of viral replication.  This results in a slow disease progression from HIV-1-infection to AIDS in the human host.  However, it is not known how the host’s ability to modulate the affects of chronic inflammation due to HIV-1 infection through the expression of moderators of inflammation affects the pace of disease progression to AIDS.  My hypothesis is that high levels of moderators of inflammation (like LAG-3, CD163, GAL-1, and HO-1) relative to the levels of mediators of inflammation (like MIP-1, IL-2, IFN-g, and TNF) decrease local chronic inflammation and immune activation resulting in slow HIV-1 disease progression.  Currently, I’m look developing optimized protocols for antibodies and riboprobes to examine this hypothesis with immunohistochemistry and in situ hybridization.  I’m also getting HIV infected human tissue and SIV infected Rhesus macaque and sooty mangabey tissue.  Macaques infected with SIV develop an AIDS like disease like humans infected with HIV, while Sooty Mangabeys do not.