Identification of Mammalian Orthoreovirus Proteins That Are Responsible for Downregulation of Hif-1a

Date
2015-04-14
Authors
Meseke, Tyler
Major Professor
Advisor
Committee Member
Journal Title
Journal ISSN
Volume Title
Publisher
Altmetrics
Authors
Research Projects
Organizational Units
Journal Issue
Series
Department
Veterinary Microbiology and Preventive Medicine
Abstract

Tumor outgrowth from the blood supply leads to low oxygen condition, or hypoxia in micro regions of solid tumors. The transcription factor, Hypoxia Inducible Factor-1 (HIF-1), regulates these hypoxic cells, and is formed when one of its components, HIF-1a, is stabilized. We previously found that Mammalian Orthoreovirus (MRV), a potent oncolytic virus, causes the downregulation of HIF-1a in infected hypoxic cells. Here we report that MRV proteins, m1 and m2 induce the downregulation of HIF-1a independent of viral infection. The ability of m2 to downregulate HIF-1a was attributed to strain specific differences, where the T1L and T3DC strains induced more downregulation than the T3DF strain. By examining single amino-acid and deletion mutants, the region containing aa 188-380, and specifically amino-acid 208 of m2, and f domain of m1 were determined to be necessary for HIF-1a downregulation. These observations provide new insights into the effects of specific MRV proteins on HIF-1a when expressed in hypoxic cells.

Comments
Description
Keywords
Citation
DOI
Source