Title

Herpes Simplex Virus Type 1 and Chlamydia Pneumoniae Infection of Astrocytes: The Effects of Co-Infection on Pathogen Replication

Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Susan T Hingley, PhD

Second Advisor

Brian J Balin, PhD

Third Advisor

Denah M Appelt, PhD

Fourth Advisor

Dawn Shell, PhD

Abstract

Despite significant advances in the medical scientific fields over the past 30 years, the etiology of many neurodegenerative diseases remains unknown. Infection is now being considered as a possible source of neurodegeneration. The evidence of inflammatory products found in many neurodegenerative disease patients is particularly remarkable, and further investigation may illuminate a link between chronic infection and neurodegeneration. This study examines two pathogens previously linked to neurodegenerative disorders, herpes simplex virus type 1 (HSV-1) and Chlamydia pneumoniae (Cpn). Human astrocytes were infected with HSV-1, Cpn, or both pathogens. During dual infection, pathogens were added simultaneously or in a staggered manner such that one pathogen was added 24 hours before the second. The infection was analyzed through immunofluorescent (IF) labeling, real-time polymerase chain reaction (RT-PCR), reverse transcriptase RT-PCR (RT2-PCR) and viral plaque assay. Our data indicate slight, but not extensive inhibition of HSV-1 replication in the presence of Cpn. Cpn replication was not prevented during dual infection, though the extent of possible inhibition is difficult to evaluate due to the complexity of the Cpn replication cycle. Astrocytes were simultaneously infected with both pathogens; the presence of one pathogen did not prevent intracellular replication of the other. Astrocytes also showed a drop in host cellular mRNA synthesis when exposed to HSV-1 for 48 hours, which is lessened in the presence of Cpn, suggesting the effect of HSV-1 on host cells may be modified by Cpn.

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