Full Name
Dr. Zeineb Mhamdi
Job Title
Postdoctoral Fellow
Company
Vaccine and Infectious Disease Organization/University of Saskatchewan
City (Work Address)
Saskatoon
State/Province/County (Work Address)
SK
Speaker Bio
Dr. Zeineb M’hamdi, Ph.D. is a Post-Doctoral Fellow at the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan. Her research focuses on the role of the host response in viral pathogenesis, with a particular interest in emerging viruses, such as influenza, Ebola, and SARS-CoV-2. She has experience with flu respiratory viruses. She uses cell and molecular biology technologies, as well as different animal models to evaluate new antiviral molecules and elucidate mechanisms of resistance to antiviral agents. Dr. M’hamdi graduated from the School of Engineering (Tunisia; 2013) and received a master’s in veterinary science, option “Virology and Infectious Disease” from Montreal University (2017) and Ph.D. (2021) in Microbiology and Immunology from Laval University Medical School, Canada.
Abstract Title
Impact of the Baloxavir-Resistant Polymerase Acid I38T Substitution on contemporary A/H3N2 virus replication and transmission in guinea pigs
Abstract Summary
Introduction. Baloxavir marboxil (BXM), licensed in 2018 by the FDA, is an antiviral targeting the highly conserved cap-dependent endonuclease region of the polymerase acidic (PA) gene. The PA/I38T substitution is a dominant marker of BXM resistance in seasonal influenza viruses. The public health risk posed by viruses with reduced susceptibility to BXM depends on their potential capacity to replicate and transmit in the community compared to susceptible viruses. Objectives. We evaluated the impact of the PA/I38T substitution on the fitness of a contemporary influenza A(H3N2) virus. Methods. Influenza A/Switzerland/9715293/2013 (H3N2) wild-type (WT) virus and its I38T mutant were rescued by reverse genetics. Replication kinetics were compared using ST6GalI-MDCK and A549 cells and infectivity/contact transmissibility were evaluated in guinea pigs. Nasal wash (NW) viral titres were determined by TCID50 ml−1 in ST6GalI-MDCK cells. Competition experiments (WT: I38T) were performed and the evolution of viral population was assessed by droplet digital RT-PCR. Results. I38T did not alter in vitro replication. I38T induced comparable titres vs the WT in guinea pigs NWs and the two viruses transmitted equally by direct contact. However, a 50 %:50 % mixture inoculum evolved to mean WT/I38T ratios of 71 %:29 % and 66.4 %:33.6 % on days 4 and 6 post-infection (p.i.), respectively. Conclusions. Contemporary influenza A(H3N2)-I38T variants may conserve a significant level of viral fitness warranting the need for active surveillance studies.
Zeineb Mhamdi