Athulya Ram

School of Mathematics 

will defend a doctoral thesis entitled,

Antigenic cooperation and cross-immunoreactivity

Tuesday, July 16 at 01:00 p.m.

Dissertation Defense Room (Price Gilbert 4222)

https://gatech.zoom.us/j/99167146884?pwd=ekDVqcXcGhnsFPaeDPRestxKUHTt81.1

Meeting ID: 991 6714 6884

Passcode: 272327

Advisor:
Prof. Leonid Bunimovich – School of Mathematics (advisor)

Committee

• Prof. Rachel Kuske – School of Mathematics

• Prof. Christine Heitsch – School of Mathematics

• Prof. Sung Ha Kang – School of Mathematics

• Prof. Will Ratcliff – School of Biology

Abstract

The evolution of RNA viruses such as Hepatitis C, HIV, and Influenza are characterized by high mutation rates that lead to a quasi-species of viral variants within each host, forming a complex ecosystem under the influence of the host immune system. Challenging traditional models that view viral evolution as a straightforward immune escape mechanism, we use a novel nonlinear ordinary differential equation model that emphasizes antigenic cooperation and cross-reactivity of host immune response. Under cross-immunoreactivity, viral variants assume different roles, most importantly persistent variants who persist through the infection by hiding from the host immune system and altruistic variants who draw the immune response to themselves and help shield the persistent variants. The role of a viral variant in this immune escape mechanism is not an inherent property of the variant, and changes based on the dynamic changes in the quasi-social ecosystem of the virus such as the emergence of a new viral variant or the merging of two intra-host viral populations through a viral transmission between a pair of infected hosts. We explore the interactions between altruistic variants shielding persistent variants from the host immune system and discover that each altruistic variant in a cross-immunoreactivity network operates independently from each other. Connections between altruistic variants change neither their qualitative roles, nor the quantitative values of the strength of persistent variants that they can shield from the host immune system. Variants strongly compete with each other to become persistent, and altruists have a maximal load for variants that they can shield from the host immune system. We also investigate cross-immunoreactivity networks derived from real Hepatitis-C patient data and find that acute and chronic phases of infection have significantly different in-degree and out-degree distributions and centralities.