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Collective Infectious Units and the Social Evolution of Viruses

Periodic Reporting for period 2 - Vis-a-Vis (Collective Infectious Units and the Social Evolution of Viruses)

Reporting period: 2018-11-01 to 2020-04-30

In contrast to the classical notion that virions function as independent infectious units, recent work has shown that viruses are often transmitted as more complex structures, such as virion aggregates, lipid vesicles, and protein matrices harbouring multiple infectious particles (“collective infectious units”). These recent discoveries set the stage for the evolution of social interactions, a previously unappreciated facet of viruses. This project investigates how collective infectious units drive virus-virus interactions. For this, we are using the conceptual framework provided by social evolution theory, which has been previously validated in different types or organisms, but not in viruses. Our model systems are enteroviruses, vesicular stomatitis virus, and baculoviruses, and we complement experimental work with simulations and modeling. We plan to explore the implications of virus collective spread for understanding and managing viral genetic diversity, transmission, evolvability, and virulence. It is becoming increasingly recognized that parasite sociality is a disease determinant, and our results may therefore inspire new antiviral strategies. This project aims at laying the foundations of sociovirology and its implications using a mechanistically-informed, bottom-up approach.
We have characterized the process of virion aggregation in vesicular stomatitis virus and how this leads to the emergence of collective infectious units. Achieving this goal has allowed us to examine the implications of collective spread for viral short-term fitness and for virus evolution. We have found that virion aggregation accelerates the early stages of the cellular infection cycle, a finding with potential implications for understanding virus infectivity during host-to-host transmission. We have also found that aggregation tends to promote the spread of cheater viruses such as defecting interfering particles. On the other hand, our experimental results and simulations suggest that genetic complementation among viruses coinfecting a cell is not a major mechanism promoting collective spread in viruses. We have also shown that, in enteroviruses, collective spread mediated by extracellular vesicles containing pools of virions does not support the ongoing cotransmission of different virus genetic variants, since each vesicle tends to encapsulate only sibling genomes from a given cell. We suggest that exclusion of unrelated viruses prevents invasion of the population by cheater viruses. Finally, we have investigated virus innate immunity evasion from a social evolution perspective. This has allowed us to demonstrate that inhibition of interferon secretion is a social trait, whose evolution depends critically on genetic relatedness among viruses present in a given host and on the spatial structure of infection and immunity.
We have, for the first time, applied Hamilton rule to a virus and, more specifically, to the evolution of viral innate immunity evasion. This brings together concepts from the fields of social evolution and virology and should inspire further work in this direction. We plan to investigate this process from a biophysical approach, combining diffusion-reaction models and cell automata simulations to describe viral spread and innate immunity responses in space.

We have demonstrated and characterized the process whereby collective infectious units arise from free virions in a model virus (vesicular stomatitis virus), and we have found that this process is triggered by saliva, a natural shedding route for this and other viruses. We now plan to better understand how saliva drives virion aggregation at the molecular level.

We have also demonstrated for the first time an Allee effect in a virus. This effect consists in a positive relationship between the number of viral genomes attacking a cell and the per-capita fitness of the virus. Our unpublished data suggest that this effect occurs in different types of viruses. We now plan to propose a general model for the existence of this Allee effect. This could change our view of how viruses invade cells.

Recent work has shown that different types of viruses are transmitted as pools of virions enclosed in extracellular vesicles. However, how many infectious particles per vesicle are harbored by these vesicles and how many genetic variants of the virus can be cotransmitted in this way remained an open question. We have addressed this using an enterovirus as model system. We now plan to establish the genetic basis of enterovirus transmission in vesicles.