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Title: Role of filamentous virion morphology during influenza virus infection
Author: Huq, Nafisa Nazmun
ISNI:       0000 0004 8504 8758
Awarding Body: University of Kent
Current Institution: University of Kent
Date of Award: 2018
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Influenza A virus is a very important pathogen as it can cause both health and economic burden around the world. It causes annual epidemics and occasional pandemics. IAV is a negative sensed enveloped RNA virus. Influenza is pleomorphic in nature, meaning it can form different morphologies, mainly spherical and filamentous. Filamentous viruses are well documented, but how and why they form is still not known. However, it is known that filamentous viruses enter host cells by macropinocytosis, while spherical viruses mostly enter by clathrin mediated endocytosis (Rossman et al., 2012). Both host and viral factors can have a role in the formation of the morphology of the virions. It is also believed that host factors can also have an effect on infectivity of the virus. In this study, the focus was on how viral morphology can affect innate immune response at early stages of infection. It was shown that filamentous virions can reduce the activation of the NF-kB thus reducing its signalling. As NF-kB is one of the first responders of the host's immune system, this means filamentous virions can successfully reduce the effects of the innate immune system during early infection. Here, we tried to find the steps that the filaments follow to bring about this reduction in activity. Influenza virus uses clathrin mediated endocytosis and macropinocytosis to enter host cells. When both the pathways are blocked it was thought that infection should decrease. However, it was noticed that blocking clathrin mediated endocytosis and micropinocytosis increases infectivity of spherical viruses. We are proposing that IAV can enter cells by a third pathway. It had been proposed that some non-infectious filamentous virions exist. The main purpose of these viruses is suggested to be to prime host cells, for increasing the cellular entry rate of the infective virions which follow it. It has been shown in this study that this concept is not true and priming of host cells beforehand does not help with consecutive infection. Understanding the morphology of filaments is a complex process. This study looked at filamentous virion's infectivity through cellular entry and the effects of host's innate immunity.
Supervisor: Rossman, Jeremy Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available