THE ROLE OF MAPK P38 STRESS PATHWAY-INDUCED CELLULAR TRANSLATION IN HUMAN AND MACAQUE CELLS TARGETED DURING B VIRUS INFECTION

• Main Author: Cook, Morgan
• Format: Others
• Published: ScholarWorks @ Georgia State University 2016
• Subjects: Herpesvirus; eIF4E; Protein translation; Virus replication; ICP6; Us3
• Online Access: http://scholarworks.gsu.edu/biology_diss/163; http://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1169&context=biology_diss

Herpes B virus, otherwise known as Macacine herpesvirus 1, is a member of the family Herpesviridae, subfamily Alphaherpesvirinae, genus Simplex, and is closely related to human herpes simplex viruses 1 and 2 (HSV1 and HSV2). B virus is endemic in macaque monkeys, but is capable of zoonotic transmission to humans resulting in fatality in greater than 80% of untreated cases. The goal of our lab is to understand the disparity in the outcome of infection between the natural host- macaques and the foreign host- humans. An important barrier to progress is the lack of understanding of host cell: B virus interactions in response to infection. An important pathway activated by stress, known as the mitogen activated protein kinase (MAPK) p38 pathway, is activated by B virus infection. Of particular interest is its role in regulating cellular translation via stimulation of activation of the eukaryotic initiation factor 4E (eIF4E). The activation of eIF4E is a vital rate-limiting step in translation, which can be manipulated by a variety of viruses. For example HSV1 can activate eIF4E through the p38 pathway but in the absence of this pathway eIF4E activity and viral titers are decreased. Because of the effect HSV1 has on the p38 pathway, and because B virus is a close relative of HSV1, we hypothesized that B virus also utilizes the p38 pathway to activate eIF4E in a host-dependent manner. In this dissertation, we show that the role of MAPK p38 with regard to translation is crucial to cellular processes that reduce virus replication in natural host cells, but within human cells this stress pathway appears not to play a role in reducing B virus replication. Data generated for this dissertation suggest that the p38 pathway is responsible in part for controlling the virus infection and spread within the natural host, but does not dampen virus replication in human host cells encountering the virus. Taken together, our results suggest that this pathway has at least one host-specific defense to combat B virus infection and that both cellular and viral proteins require the presence or absence of this pathway to function.