Transmission of Influenza A Virus Genomic Diversity Between Human Hosts Open Access

Berg, Nicolas (Spring 2021)

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Defective interfering particles (DIPs) are viruses containing a genetic abnormality wherein a large portion of the genome is deleted, rendering them incapable of independent reproduction. However, during a coinfection event between a wild-type virus and a DIP, the defective virus can hijack functional components from its counterpart and reproduce. This ‘viral parasitism’ has important effects on the within-host dynamics of many infections and has been shown to reduce symptom severity and infectivity. Exogenous administration of DIPs into a host is a current area of medicinal research as a promising anti-viral therapeutic. In this study, the possibility of transmission of defective interfering influenza virus is explored using whole-genome sequencing data of virus samples contained within verified household transmission pairs. Deletions characterizing DIP genomes were documented using a custom software pipeline, and various properties such as location and length were compared across groups. It was found that there was no significant relationship between transmission linkage and increased occurrence of shared deletions, lending support to the stochastic generation of identical DIPs across hosts rather than transmission.

Table of Contents


Introduction                                                                                                                          1-4

Methods                                                                                                                                5-9

           Influenza Virus Sequencing Data                                                                               5

           Identification of DVGs                                                                                                6

           Mapping of Deletions                                                                                                7

           Data Filtration                                                                                                            8

           Analysis of Data                                                                                                         8

Results                                                                                                                                   10-21

           Read Depth                                                                                                                10

           Volume of Detected Deletions                                                                                  11

           Lengths of Deletions                                                                                                  14

           NS Segment Recurring Deletion Profile                                                                     16

           Longitudinal Analysis                                                                                                 18

           DVG Transmission Analysis                                                                                        20

Discussion                                                                                                                              22-24

References                                                                                                                             25-27

Supplementary Materials                                                                                                    28

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