Antigenic cooperation in Viral Populations: Transformation of Functions of Intra-Host Viral Variants

TL;DR

This paper explores how intra-host viral populations adapt through antigenic cooperation, allowing viruses to escape immune responses and establish chronic infections by dynamically reorganizing their roles within a viral ecosystem.

Contribution

It introduces a novel mechanism of immune escape via antigenic cooperation, providing analytical and numerical insights into viral adaptation and population merging in chronic infections.

Findings

Viral variants can rapidly re-arrange roles during immune escape.

Transmission between hosts merges viral populations into stable immune-adapted states.

Antigenic cooperation can lead to stable chronic infection states.

Abstract

In this paper we study intra-host viral adaptation by antigenic cooperation - a mechanism of immune escape that serves as an alternative to the standard mechanism of escape by continuous genomic diversification and allows to explain a number of experimental observations associated with the establishment of chronic infections by highly mutable viruses. Within this mechanism, the topology of a cross-immunoreactivity network forces intra-host viral variants to specialize for complementary roles and adapt to host's immune response as a quasi-social ecosystem. Here we study dynamical changes in immune adaptation caused by evolutionary and epidemiological events. First, we show that the emergence of a viral variant with altered antigenic features may result in a rapid re-arrangement of the viral ecosystem and a change in the roles played by existing viral variants. In particular, it may push the population under immune escape by genomic diversification towards the stable state of adaptation by antigenic cooperation. Next, we study the effect of a viral transmission between two chronically infected hosts, which results in merging of two intra-host viral populations in the state of stable immune-adapted equilibrium. In this case, we also describe how the newly formed viral population adapts to the host's environment by changing the functions of its members. The results are obtained analytically for minimal cross-immunoreactivity networks and numerically for larger populations.