Antigenic cooperation in viral populations: Transformation of functions of intra-host viral variants.

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 the 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 the 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.

Local Immunodeficiency: Combining Cross-Immunoreactivity Networks.

This article continues the analysis of the recently observed phenomenon of local immunodeficiency (LI), which arises as a result of antigenic cooperation among intrahost viruses organized into a network of cross-immunoreactivity (CR). We study here what happens as the result of combining (connecting) the simplest CR networks, which have a stable state of LI. It turned out that many possibilities occur, particularly resulting in a change of roles of some viruses in the CR network. Our results also give some indications about a boundary of the set of CR networks with stable state of LI in the entire collection of all possible CR networks. Such borderline CR networks are characterized by only a marginally stable (neutral rather than stable) state of the LI, or by the existence of such subnetworks in a CR network that evolve independently of each other (although being connected).