Nancy J. Bigley (Advisor), Marjorie Markopoulos (Committee Member), Dawn P. Wooley (Committee Member)
Master of Science (MS)
Herpes Simplex Virus Type 1 (HSV-1) infection occurs through the epithelial cells of the skin or mucous membranes. The beginning of the primary infection is rapid and is characterized by pain in the mouth, salivation, and submandibular lymphadenitis. The infected mucosa produces numerous, small and red lesions known as cold sores, however, many cases are asymptomatic. After the primary infection HSV-1 moves through the nerve to stay in trigeminal ganglia and to cause a recurrent infection from time to time. In the early hours of the HSV-1 infection, the cytokines produced by infected cells are critical in the stimulation of the innate immune response to the infection. One of the innate immune cells responded to the infected cells is macrophages. So, macrophage recruitment and differentiation are essential for effective control and clearance of viral infections. To mimic the in vivo role of three types of macrophages against HSV-1 infected epithelial cells (PAM 212), M0, M1, or M2 RAW246.7 macrophages were added at 2 and 4 hours after an initial established infection. These times were selected to represent the influx of macrophages to the infection site within the first few hours of exposure to HSV-1 virus. In all experiments, we performed cell viabilities and virus titers at 24, 48, and 72 hours after the initial infection. After the HSV-1 infection, a morphological change was observed among all types of macrophages where most of it appeared round and granulated. This change makes it challenging to differentiate M1 from M0 or M2. Importantly, all phenotype of macrophages showed an essential role against the HSV-1 replication in PAM-212 keratinocytes. However, the addition of M1 Macrophages to HSV-1 infected PAM212 keratinocytes significantly decreased the percentage of the viable cells by more than 80% and restricted the HSV-1 replication more effectively than M0 and M2 macrophages. The virus replication pattern was similar in a different type of M2 macrophages (M2 a and M2 c) which was low at 24 h, then increased significantly 48 hpi then decreased significantly 72 hpi.
Department or Program
Microbiology and Immunology
Year Degree Awarded
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