Photo: electron micrograph of West Nile virus by Cynthia Goldsmith, USCDCP on Pixnio Feb 2022 

Photo: adapted from today.cofc.edu/wp-content/uploads/2019/07 Preface: Key Concepts in Evolution ⁍ “Survival of the fittest” ⁍ Natural selection determines which genes are passed on through the generations ⁍ Random genetic mutations can give rise to novel phenotypes 

Red Queen Hypothesis Photo: commons.wikimedia.org/wiki/Category:Lotka–Volterra_equations Evolution between species driven by predator/prey dynamics1,2 Photo: © Words & Unwords from zazzle.com 

Black Queen Hypothesis ⁍ Theory of reductive evolution1,2 ⁍ Loss of redundant genes where a population’s resources are pooled (“public goods”)1,2 ⁍ Members of population experience cost/benefit trade- offs Photo: plektix.fieldofscience.com 

⁍ Gene-centered view of evolution3 ⁍ Fundamental units of natural selection3: 1. Gene, or “replicator” 2. Organism, or “vehicle” ⁍ Genes act to replicate themselves and those most similar3 The Selfish Gene Theory Photo: crickhollowbooks.com.au 

Social Evolution Theory ⁍ Originally developed to explain animal behavior ⁍ Explains social behavior in terms of evolution4 ⁍ Can be applied to microorganisms4 Photo: “Sociobiology: The New Synthesis.” Wilson, Edward O. Cambridge MA: Belknap Press of Harvard University Press, 1975. Accessed from raptisrarebooks.com. 

Social Evolution Theory Photo: “Sociobiology: The New Synthesis.” Wilson, Edward O. Cambridge MA: Belknap Press of Harvard University Press, 1975. Accessed from raptisrarebooks.com. ⁍ Cooperative traits that benefit others are favored by natural selection if they benefit the fitness of the individual performing them5. ⁍ Cooperative traits cannot evolve merely by providing a benefit to a population5. 

⁍ Microbes are known to communicate and coordinate behavior5: – Quorum sensing – Biofilm formation – Chemical warfare Social Evolution Applied to Microbiology Photo: CC BY-NC-SA 3.0 "An electron microscopy image shows an E. coli biofilm" North Dakota State University. https://www.ag.ndsu.edu/news/newsreleases/2011/april-25-2011/ndsu-researcher-studies- disease-causing-bacteria/an-electron-microscopy-image-shows-an-e.coli-biofilm/view E. coli forming a biofilm 

⁍ Viruses have been observed to interact5: – Co-infecting viruses – Bacteriophages communicate to regulate cell lysis ⁍ Behave more in accordance with the Selfish Gene Theory Social Evolution Applied to Virology​ ? Sociovirology T2 phages attached to E. coli cells Photo: © Lee D. Simon on pixels.com 

Sociovirology “ ⁍ Socio-” implies: – Anthropomorphic – Personal motives – Political motives Photo: vecteezy.com 

“ ⁍ Socio-” implies: – Anthropomorphic – Personal motives – Political motives Sociovirology ⁍ Behavior is algorithmic Photo: adapted from youtube.com/watch?v=mpLkNIf-Wxo 

Sociovirology ⁍ Arguably, viruses aren’t even alive6 – Replicates only within living cells by pirating cellular machinery – Principal biological function is to replicate Photo: adapted from youtube.com/watch?v=mpLkNIf-Wxo 

⁍ Players: Viruses ⁍ Goal: self-replication ⁍ Challenge: viral gene transmission at cost to host The “Game” Photo: © 2000, American Society for Microbiology 

Photo: electron micrograph of hepatitis by USCDCP on Pixnio And now, onto the article 

Definition of an “Individual” DNA virus: single infectious viral genome. Example: adenovirus RNA virus: due to high mutation rate, consensus sequence or “quasispecies.” Example: coronavirus Coronavirus From Figure 2 on pediaa.com/difference-between-dna-and-rna-viruses From Figure 5, Mandary et al., 2019 on mdpi.com Adenovirus 

Interactions Between Individuals 

(A.) Production of public goods through transcription/translation and sharing of viral products needed for replication. Interactions Between Individuals 

(B.) Blocking the entry of other viruses into the cell, especially those with low genetic similarity. Interactions Between Individuals 

(C.) Inducing host immune changes that favor the transmission of all viruses. Interactions Between Individuals 

(D.) Inducing host cell to produce molecules essential for viral transmission to neighboring cells. Interactions Between Individuals 

(E.) Communicating cell infection status, signaling the availability of host cells for infection. Interactions Between Individuals 

(F.) Manipulating host immune signals to induce distant cells to differentially express receptors favoring entry of some viruses over others. Interactions Between Individuals 

Social Evolution Framework ⁍ Social interactions between viruses occur when the traits of one individual influence the fitness of another. – Driven by natural selection ⁍ Exist on a spectrum: Conflict Cooperation 

Conflict Occurs more frequently with: – Decreasing genetic relatedness – Increasing competition – Diverging evolutionary interests – Greater genetic diversity between viruses infecting the same host, also called multiplicity of infection (MOI) 

Conflict Can lead to emergence of “selfish” behavior or “cheats” – Optimizes its own fitness in coinfections – Contributes few or no public goods – Parasitism – Reduces average population fitness 

Conflict Example of “selfish” behavior in defective interfering particles (DIP): – Viruses with large deletions in genome – Require “helper” viruses to reproduce – Act as virus parasites, cause net depletion of population’s resources – Numbers increase with increasing diversity of MOI Defective interfering particles of Semliki Forest virus (a) vs. standard Semliki Forest virus (b) Photo: Barrett et al. 1984 

Cooperation Occurs more frequently with: – Increasing genetic relatedness (kin selection) – Decreasing competition – Shared interests – Mutual compensation for genetic defects (genetic complementation) 

Cooperation Can lead to emergence of “heterotypic cooperation” – Mutually beneficial cooperation between genetically distinct individuals – Overall population fitness increases with higher incidence of cooperation – Found in viruses that act as co- infections, such as influenza viruses 

Cooperation Example of heterotypic cooperation in influenza viruses: – One strain has a more efficient hemagglutinin (cell adhesion) – Another has a more efficient neuraminidase (release of virions) H1N1 influenza virus Photo: Micrograph of H1N1 by CDC from cbc.ca 

The Problem of Cooperation = Cooperator. Individual performing cooperative action. = Selfish cheater. Does not perform cooperative action. 

The Problem of Cooperation ⁍ A selfish cheater arises in a population through mutation or coinfection. ⁍ Benefits from cooperative behavior of cooperators without contributing. 

The Problem of Cooperation ⁍ The selfish cheater increases frequency in subsequent generations. ⁍ The result is a reduction of average population fitness. 

Testing Social Interactions Using Social Evolution Theory ⁍ Strains made to compete in isolation and in combination to quantify fitness and confirm social traits. 

Testing Social Interactions Using Social Evolution Theory ⁍ When grown as a single infection, a population of cooperators observed to achieve higher growth than a population of cheaters. 

Testing Social Interactions Using Social Evolution Theory ⁍ In coinfection, population growth observed to be lower than a homogeneous population of cooperators. 

Testing Social Interactions Using Social Evolution Theory ⁍ Cheater constituents within the coinfection population initially increase growth by exploiting the cooperator constituents; in time growth stalls as the population is dominated by cheaters. Constituent population of cheaters Constituent population of cooperators 

Conclusions ⁍ Viruses are observed to have social interactions that can be understood using social evolution theory ⁍ Targeting virus-virus interactions can lead to new treatment strategies – Attenuated vaccines of DIPs could increase cheating behaviors and reduce fitness of virus populations – Epidemiologists could consider the population fitness effects of “cheating” to predict the best strategies for limiting transmission of infectious viruses – Knowledge of bacteriophage interactions could improve phage therapy 

References 1. Morris, J. J., Lenski, R. E., & Zinser, E. R. (2012). The Black Queen Hypothesis: evolution of dependencies through adaptive gene loss. mBio, 3(2), e00036-12. https://doi.org/10.1128/mBio.00036-12 2. Mas, A., Jamshidi, S., Lagadeuc, Y., Eveillard, D., & Vandenkoornhuyse, P. (2016). Beyond the Black Queen Hypothesis. The ISME journal, 10(9), 2085–2091. https://doi.org/10.1038/ismej.2016.22 3. Dawkins, R. (2006). The Selfish Gene. Oxford University Press. 4. West, S., Griffin, A., Gardner, A., Diggle, S. P. (2006). Social evolution theory for microorganisms. Nat Rev Microbiol, 4, 597–607. https://doi.org/10.1038/nrmicro1461 5. Díaz-Muñoz, S. L., Sanjuán, R., & West, S. (2017). Sociovirology: Conflict, Cooperation, and Communication among Viruses. Cell host & microbe, 22(4), 437–441. https://doi.org/10.1016/j.chom.2017.09.012 6. Koonin, E. V. & Starokadomskyy, P. (2016). Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Stud Hist Philos Biol Biomed Sci, 59, 125-34. https://doi.org/10.1016/j.shpsc.2016.02.016