Epigenetic Landscape during Coronavirus Infection

Epigenetic Landscape during Coronavirus Infection

Alexandra Schäfer and Ralph S. Baric

Coronaviruses (CoV) make up a large group of human and animal pathogens. Two of the most familiar coronaviruses include SARS-CoV (severe respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus. Recently, studies show that viruses have complex processes that regulate the host epigenome and control innate antiviral defense processes, allowing for virus replication and pathogenesis. This paper looks at emerging coronvirus infections and the resulting new viral defense mechanisms.

Coronaviruses are enveloped RNA viruses and the viral particles are surrounded by ‘spike’-shaped glycoproteins, which give the viruses their characteristic microscopic ‘corona-like’ appearance. Both pathogens cause respiratory tract infections, with the most impacted individuals developing acute respiratory distress syndrome (ARDS).  Asymptomatic infections were rare during the SARS-CoV epidemic, MERS-CoV infections frequently result in asymptomatic infections leading to asymptomatic spread--similar to the asymptomatic spread of COVID-19 currently. 

As we discussed last week, Epigenetics is the study of any potentially stable and, ideally, heritable change in gene expression or cellular phenotype that occurs without changes in the underlying DNA. Viruses interfere with epigenetic regulatory programs within the host, such as histone modification, chromatin remodeling, and viral proteins that interact with the modified histones. Prior studies have noted viruses impacting the immune response by altering the epigenetic gene expression (turn on and off). The evolution of viral defenses and epigenetic effects that allow viruses to attack gene clusters, should be studied in the future.

I sent this paper out as a follow-up, but after reading the book, I thought it would be interesting to post about. This paper goes over two different coronaviruses, SARS-CoV (2002/2003) and MERS-CoV (2012), and touches on the selective pressure that increases the adaptability of the pathogen as a marker of success. Co-evolution is an important mechanism to ensure the viability within a host (and their immune response). Additionally, it is an in-depth article covering epigenetic mechanisms, gene activation and expression, and using epigenetics as a way to identify genes and develop antiviral drugs.

IMAGE: Epigenetic modification infection with highly virulent respiratory viruses--changes in the base state of host chromatin. Infection with H1N1-09 and SARS-CoV results in enrichment of H3K4me3 incorporation (green ovals) and depletion of H3K27 (red diamonds), and therefore in open, transcription-active chromatin. In contrast, H5N1-VN1203 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection drives H3K27me3 enrichment and depletes H3K4me3 for a subset of genes, favoring a closed chromatin conformation that inhibits interferon-stimulated gene (ISG) expression


Kailie Batsche
Potluck for 14 April 2020
Link: https://www.ncbi.nlm.nih.gov/pubmed/28212305

Pervasive Natural Selection in the Drosophila Genome?

Evidence from the Drosophilia genome suggest that they are undergoing purifying selection. In the article Sella et al. use genomic data from the different Drosophila species, including D. melanogaster and D. simulans, D. virilis, D. americana, D. miranda and D. pseudoobscura. The genome encodes the heritable phenotype of an organism so patterns of variation within and between species can provide answers to these questions, as well as help characterize the intensity and rate of adaptation. Numerous studies have estimated that 40–50% of the amino acid substitutions in Drosophila species are adaptive but they are not clustered in particular subsets of genes. Estimates indicate that Drosophila species experience an adaptive amino acid substitution every 200–400 generations and one in non coding regions at potentially more than five times that rate. In the end Sella et al. determined that most of the genome is under purifying selection and a large fraction of divergence at amino acid, and non coding regions, is beneficial. As well as the dynamics of neutral and weakly selected alleles are affected substantially by selection at linked sites.

https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000495

Potluck Post- 4/13/2020
Annelise Beer

Rapid Evolution in a Human Innate Immune Receptor

Adrian et al. examine a family of receptor molecules, known as CEACAM, which enable bacterial pathogenic colonization. A particular phagocytic receptor, CEACAM3, can attack bacterial pathogens and has been shown to be under strong positive selection, with a high number of nonsynonymous mutations compared to synonymous mutations. Their research suggests that this family of innate immune receptors appeared after Old World monkeys split from other primates. Within the human lineage, CEACAM3 has developed mutations that allow it to detect and bind species-specific human restricted bacteria. Furthermore, different populations around the world are shown to have varying degrees of polymorphisms suggesting regional selection. Future research into the less-studied world of other great ape specific bacterial pathogens would help add to the understanding of this receptor family. 

Audrey Tjahjadi

Link to original article: https://www.cell.com/current-biology/pdfExtended/S0960-9822(19)30087-9

BMC Evolutionary Biology Update: Red Queen Dynamics

This paper addresses the mathematics of modelling red queen oscillations. Specifically the interactive effective of red queen dynamics, and ecological dynamics which previously has not been addressed fully. They show that the time taken for extinction (the time for a genotype to me lost), is faster when populations size are smaller, competition is on a local scale and variation in population size is taken in to account. This illustrates that larger population although increasing levels of intra-specific competition can help dampen the effects of inter specific competition and red queen dynamics. It also demonstrates the benefit of breeding with populations outside of your immediate core area.

Jack Richardson - Journal update
Link to paper: https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-019-1562-5

The Behavioural Immune System

 Living in social societies creates many benefits to survival. Traditionally it benefitted us in reducing predation risk, increasing access to food and improving offspring care. In the modern world all of these benefits remain true however we often depend on people we don't know to help us in achieving these tasks, additionally the modern world depends on social contact for learning, cooperation and development. Despite these advantages social contact, increases our exposure to pathogens. The behavioural immune system suggests that we have evolved to socially distance from people that are sick, including the development of our emotional 'disgust' for people that are symptomatic. This extends further in some eusocial invertebrate that actually swap mucous to spread antibodies in a immunisation type event. Arguments have also been made that 'sickness behaviour' is also a warning for other to stay away, as we inherently avoid people that show signs of illness.

Discussion questions:

Is our behavioural immune system responses no longer sufficient to prevent disease spread in the societies we live in?
Is there a level of social contact and disease transmission that is beneficial to improve overall immunity to common diseases?
At what point do the benefits of social contacts outweighs the costs of increased disease transmission?


Jack Richardson - Potluck
Link to article: https://www.frontiersin.org/articles/10.3389/fpsyg.2019.01004/full

Journal Update 3/5: What is creating the height premium?

During this study Wang et al uses a Mendelian randomization approach to try and identify a relationship between height and earnings. They did this by collecting genetic data and sociodemographic information from 3,427 people in mainland China. Apparently unbeknownst to me, an average height person, height is believed to be a key to success. This study exploits variation in individual's genetic markers and polygenic risk scores to use within the framework of Mendelian randomization. In the end they determined that height does, or seems to, play a role in the job market and they also identified personality traits and other genetic markers (such as depression) that can affect your job opportunities. They state that this height may act as a signal of beneficial circumstances for developing higher cognitive/non-cognitive skills during childhood or early-life. Great, so I just need some of those bucket stilts to stand on and I will be forever successful... just kidding!

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230555

Journal update 3/5 
Annelise Beer 4/12/2020

Testing for paternal influences on offspring telomere length in a human cohort in the Philippines

Testing for paternal influences on offspring telomere length in a human cohort in the Philippines

Dan T. A. Eisenber, M. Geoffrey Hayes, Peter H. Rej, Paulita Duazo, Christopher W. Kuzawa

This article discusses the shortening of telomeres, the ends of chromosomes that shorten with cell division, age, stress, and even environmental exposure. Telomere shortening has been linked with spaceflight in the past (i.e. NASA study on the Kelly brothers); however, telomere length is thought to be selected against due to negative effects on health and longevity, cause impaired immune function, and deterioration with age. This article discusses the possible effects of paternal experiences on telomere length in human offspring. Sperm telomeres lengthen with age, as well as plasticity, but oxidative stress indicates a shortening. For this multigenerational study, they first look at the connection between telomere length in adult offspring and paternal smoking; however, they observe a correlation between paternal knee height (a measure of nutritional health as a child/infant) and stress in the fathers.

They found that decreased paternal knee height predicted longer offspring telomere length, opposite of their predictions. They found no correlation between smoking or stressors to offspring telomere length. They note that knee height may be the physiological effects of developing testes and germ cells (earlier puberty=longer telomeres, shorter leg length, and longer trunk), or correlated with biological, genetic, or social pathways that could have an effect on telomere length.

I thought this article was interesting due to the different genetic, social, and environmental effects on telomere length, especially in light of the Kelly spaceflight study.

Kailie Batsche

March AJPA update

Link: https://onlinelibrary.wiley.com/doi/10.1002/ajpa.23983