Exploring Nipah virus strain differences through use of recombinant and chimeric viruses as well as utilization of a novel 3D human lung model

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes lethal encephalitis and respiratory illness in humans. There are two variants of NiV - NiV Malaysia (NiVM) and NiV Bangladesh (NiVB). Despite high sequence homology between the strains, there are several key differences in epidemiological and pathobiological features. The reasons for these differences have not been thoroughly investigated and this dissertation seeks to address this gap. In addition to constructing a reverse genetics system for NiVB (rNiVB) to complement the previously available system for NiVM, a panel of chimeric NiVs expressing the fusion (F), attachment glycoprotein (G), and matrix (M) proteins of the alternate variant alone or in combination was generated. These chimeric viruses were evaluated in in vitro systems representing many of the primary cellular targets of NiV infection. While there appears to be no significant differences between wildtype NiVM and the rNiVM/NiVB-F and -G bearing chimeras, recombinant chimeras bearing the M protein of the other strain displayed differences in plaque phenotype, replication kinetics, fusogenicity, and budding in a cell type-dependent manner. Additionally, a 3D human lung microphysiologic human organ culture model for NiV infection was established and utilized to compare NiV strains as well as describe immune response.

Name thesis:degree_name

Microbiology and Immunology (Doctoral)

Discipline thesis:degree_discipline

Microbiology

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2023

Author dc:creator

• Johnson, Kendra Nicole

Advisor dc:contributor.advisor

• Freiberg, Alexander (anfreibe@utmb.edu)

Committee members dc:contributor.committeemember

• Vineet Menachery
• Ricardo Rajsbaum
• Joan Nichols
• Benhur Lee

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12844

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12844