UBC Theses and Dissertations
Rhinovirus infection of the human airway epithelium : in vitro characterization of viral replication, inflammatory response, and immunemodulating effects of echinacea Machala, Anna
Rhinoviruses (RVs) are the leading cause of upper-respiratory tract infections in humans. To date relatively little is known about the mechanism of RV infection and no cure or prevention exists. Mounting evidence shows that RV replicates very little in its host airway epithelial cells leading researchers to hypothesize that the illness associated with RV infection is the result of the host's immune response, but not necessarily RV replication. This study characterized RV infection in vitro in terms of viral replication, viral RNA, and pro-inflammatory cytokine/chemokine secretion over the course of a typical infection using two distinct airway epithelial cell lines (BEAS-2B and A549) and two different receptor-utilizing RV serotypes (RV14 and RV1A). Cells were infected with known amounts of RV, sampled over 1 week, and assayed for infectious virus, RV14 RNA, and interleukin (IL)-6 and/or IL-8 secretion. For BEAS-2B and A 549 cells viral replication peaked between day 1 (Dl) and D2 post-infection for both RV14 and RV1A, and no significant viral replication was observed after D3. Stimulation of LL-6 and IL-8 was typically not observed before D2 and remained elevated up to D7. Overall, BEAS-2B cells were more susceptible to RV infection than A549, and similar trends were observed for RV14 and RV1A, except RV14 failed to replicate in the A549 cells. Furthermore, UV inactivation of both RV serotypes completely inhibited viral replication and IL-6 secretion in the BEAS-2B model, suggesting the necessity of genetically intact virus to stimulate the IL-6 response. Finally, the effects of two chemically distinct Echinacea extracts on viral replication and IL-6 secretion were investigated in the BEAS-2B model. Neither of the Echinacea extracts had any effect on RV replication, nor did they stimulate IL- 6 secretion in uninfected cells. However, Echinacea treatment of RV infected cells significantly affected IL-6 secretion, but a different trend was observed between RV serotypes, and for the two herb preparations. Overall, RV infection of airway epithelial cells results in relatively low levels of RV replication but a pronounced proinflammatory cytokine/chemokine response which is the likely cause of cold symptoms and a potential target for therapeutics.
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