Mikyla Simones

Mikyla Simones

Mikyla Simones Majors: Biology - Biomedical & Premedicine|

Minor: Chemistry

Anticipated Graduation Date: May, 2013

Research Supervisor: Dr. Karen Klyczek, Collaborative Research with Dr. Brian Fife at University of Minnesota (Presently)

Faculty Mentor: Dr. Karen Klyczek, Biology, University of Wisconsin-River Falls

Research Location: Medical College of Wisconsin, Summer Program for Undergraduate Research (SPUR), Summer 2012

Research Topic: Human Herpes Viruses and Their Interactions with the Human Immune System

Abstract:

Effects on NK activating ligands when expressing MHV-68 orf36 kinase


Mikyla M Simones
Microbiology and Molecular Genetics Department
Medical College of Wisconsin
Milwaukee, WI

Primary Investigator: Dr. Amy Hudson

The MHV-68 orf36 kinase is an important viral kinase involved in the Murid herpesvirus 68 mouse model of Kaposi Sarcoma-associated herpesvirus (KSHV). Murid herpesvirus 68, MHV-68, is a member of the Gammaherpesvirinae and plays an important role in human disease, ie. Kaposi’s sarcoma. The orf36 MHV-68 gene encodes for phosphorylation of Krupell-associated box domain-associated protein 1. This allows a switch from latency to lytic replication, resulting in an activated DNA damage response (Terakanova et al. 2010). DNA damage response can be triggered by a number of different influences including excessive ultra-violet radiation, chemotherapeutic agents, Υ-irradiation, and/or virus evasion. When the DNA damage response occurs, numerous stress signals are released from the interferon population, proteins made and released by the host cell in the presence of pathogens. Soon following interferon activity is the surveillance of Natural Killer (NK) cells. NK cells detect NK activating/inhibitory ligands on the cell surface (Koch et al, 2012). An up-regulation of NK ligands produces an imbalanced signal resulting in cell death by the patrolling NK cells. By way of Flow Cytometry, the up-regulation of NK activating ligands ULBP1, ULBP2, ULBP3, MICA, and MICB were observed when orf36 kinase was expressed. None of the NK activating ligands tested in this experiment were detected on the cell surface, leading us to believe these NK activating ligands were not up-regulated. Expression of orf36 kinase may induce part of the DNA damage response, but somehow has adapted mechanistic strategies to prevent up-regulation of NK activating ligands on the cell surface, and possible detection from the human immune system.