hepatitis B

New research analyses the evolution of the last ten thousand years of the hepatitis B virus

The University of Valencia participates in a research on the evolution of the last ten thousand years of the hepatitis B virus

A study published in the journal Science traces the evolution of the hepatitis B virus from prehistory to the present, revealing dissemination routes and changes in viral diversity. Domingo Carlos Salazar García, researcher from the Prehistory, Archeology and Ancient History Department of the University of Valencia, has participated in this study led by the Max Planck Institute for the Science of Human History (Germany). The research uncovers the evolution of the hepatitis B virus since the Early Holocene by analyzing the largest dataset of ancient viral genomes produced to date.

hepatitis B
Domingo Carlos Salazar García, researcher from the Prehistory, Archeology and Ancient History Department of the University of Valencia

“This research puts upfront a reality many times ignored but obvious, that viruses have been linked to humans since prehistoric times”, highlighted Salazar, graduated in Medicine and in History, researcher of excellence of the Valencian Community at the University of Valencia. “If SARS-COV-2 has been able to put human societies in check worldwide during the twenty-first century, we can only begin to imagine how viral diseases influenced life in prehistoric times”, he explains. “Historians and archaeologists must start considering more the influence of viruses and other agents that until now have been invisible on the archaeological record when reconstructing past lifestyles”, he says.

The hepatitis B virus (HBV) is a major health problem worldwide, causing close to one million deaths each year. Recent ancient DNA studies have shown that HBV has been infecting humans for millennia, but its past diversity and dispersal routes remain largely unknown. A new study conducted by a large team of researchers from all around the world provides major insights into the evolutionary history of HBV by examining the virus’ genomes from 137 ancient Eurasians and Native Americans dated between ~10,500 and ~400 years ago. Their results highlight dissemination routes and shifts in viral diversity that mirror well-known human migrations and demographic events, as well as unexpected patterns and connections to the present.

Present-day HBV strains are classified into nine genotypes, two of which are found predominantly in populations of Native American ancestry. The study provides strong evidence that these strains descend from an HBV lineage that diverged around the end of the Pleistocene and was carried by some of the first inhabitants of the Americas.

“Our data suggest that all known HBV genotypes descend from a strain that was infecting the ancestors of the First Americans and their closest Eurasian relatives around the time these populations diverged”, says Denise Kühnert, leader of the research group.


HBV in prehistoric Europe

The study also shows that the virus was present in large parts of Europe as early as 10,000 years ago, before the spread of agriculture to the continent. “Many human pathogens are thought to have emerged after the introduction of agriculture, but HBV was clearly already affecting prehistoric hunter-gatherer populations”, says Johannes Krause, director of the Department of Archaeogenetics at the Max Planck Institute for Evolutionary Anthropology and co-supervisor of the study.

After the Neolithic transition in Europe, the HBV strains carried by hunter-gatherers were replaced by new strains that were likely spread by the continent’s first farmers, mirroring the large genetic influx associated with the expansion of farming groups across the region. These new viral lineages continued to prevail throughout western Eurasia for around 4,000 years. The dominance of these strains lasted through the expansion of Western Steppe Herders around 5,000 years ago, which dramatically altered the genetic profile of Europeans but remarkably was not associated with the spread of new HBV variants.


The collapse and re-emergence of pre-historic HBV

One of the most surprising findings of the study is a sudden decline of HBV diversity in western Eurasia during the second half of the 2nd millennium BCE, a time of major cultural shifts, including the collapse of large Bronze Age state societies in the eastern Mediterranean region.

“This could point to important changes in epidemiological dynamics over a very large region during this period, but we will need more research to understand what happened”, says Arthur Kocher, lead author and researcher in the group.

All ancient HBV strains recovered in western Eurasia after this period belonged to new viral lineages that still prevail in the region today. However, it appears that one variant related to the previous prehistoric diversity of the region has persisted to the present. This prehistoric variant has evolved into a rare genotype that seems to have emerged recently during the HIV pandemic, for reasons that remain to be understood.


Article: Kocher et al. “Ten millennia of hepatitis B virus evolution”, Science, 2021. DOI: https://www.science.org/doi/10.1126/science.abi5658

Press release from the University of Valencia and Asociación RUVID.

Infectious disease modeling study casts doubt on impact of Justinianic plague

Infectious disease modeling study casts doubt on impact of Justinianic plague

Work shows value of new examinations of old narratives of this pandemic

Justinianic Plague mathematical modeling
Costumes of All Nations (1882), by Albert Kretschmer, painters and costumer to the Royal Court Theatre, Berin, and Dr. Carl Rohrbach. Picture in the public domain

ANNAPOLIS, Md. - Many have claimed the Justinianic Plague (c. 541-750 CE) killed half of the population of Roman Empire. Now, historical research and mathematical modeling challenge the death rate and severity of this first plague pandemic.

Researchers Lauren White, PhD and Lee Mordechai, PhD, of the University of Maryland's National Socio-Environmental Synthesis Center (SESYNC), examined the impacts of the Justinianic Plague with mathematical modeling. Using modern plague research as their basis, the two developed novel mathematical models to re-examine primary sources from the time of the Justinianic Plague outbreak. From the modeling, they found that it was unlikely that any transmission route of the plague would have had both the mortality rate and duration described in the primary sources. Their findings appear in a paper titled "Modeling the Justinianic Plague: Comparing hypothesized transmission routes" in PLOS ONE.

"This is the first time, to our knowledge, that a robust mathematical modeling approach has been used to investigate the Justinianic Plague," said lead author Lauren White, PhD, a quantitative disease ecologist and postdoctoral fellow at SESYNC. "Given that there is very little quantitative information in the primary sources for the Justinianic Plague, this was an exciting opportunity to think creatively about how we could combine present-day knowledge of plague's etiology with descriptions from the historical texts."

White and Mordechai focused their efforts on the city of Constantinople, capital of the Roman Empire, which had a comparatively well-described outbreak in 542 CE. Some primary sources claim plague killed up to 300,000 people in the city, which had a population of some 500,000 people at the time. Other sources suggest the plague killed half the empire's population. Until recently, many scholars accepted this image of mass death. By comparing bubonic, pneumonic, and combined transmission routes, the authors showed that no single transmission route precisely mimicked the outbreak dynamics described in these primary sources.

Existing literature often assumes that the Justinianic Plague affected all areas of the Mediterranean in the same way. The new findings from this paper suggest that given the variation in ecological and social patterns across the region (e.g., climate, population density), it is unlikely that a plague outbreak would have impacted all corners of the diverse empire equally.

Xenopsylla cheopis, photo by Katja ZSM, CC BY-SA 3.0

"Our results strongly suggest that the effects of the Justinianic Plague varied considerably between different urban areas in late antiquity," said co-author Lee Mordechai, an environmental historian and a postdoctoral fellow at SESYNC when he wrote the paper. He is now a senior lecturer at the Hebrew University of Jerusalem, and co-lead of Princeton's Climate Change and History Research Initiative (CCHRI). He said, "This paper is part of a series of publications in recent years that casts doubt on the traditional interpretation of plague using new methodologies. It's an exciting time to do this kind of interdisciplinary research!"

Using an approach called global sensitivity analysis, White and Mordechai were able to explore the importance of any given model parameter in dictating simulated disease outcomes. They found that several understudied parameters are also very important in determining model results. White explained, "One example was the transmission rate from fleas to humans. Although the analysis described this as an important parameter, there hasn't been enough research to validate a plausible range for that parameter."

These high importance variables with minimal information also point to future directions for empirical data collection. "Working with mathematical models of disease was an insightful process for me as a historian," reflected Mordechai. "It allowed us to examine traditional historical arguments with a powerful new lens."

Together, with other recent work from Mordechai, this study is another call to examine the primary sources and narratives surrounding the Justinianic Plague more critically.


White, L.A. & Mordechai, L. (2020). Modeling the Justinianic Plague: Comparing hypothesized transmission routes. PLOS ONE. doi: 10.1371/journal.pone.0231256

About SESYNC: The University of Maryland's National Socio-Environmental Synthesis Center (SESYNC) in Annapolis brings together the science of the natural world with the science of human behavior and decision making to find solutions to complex environmental problems. SESYNC is funded by an award to the University of Maryland from the National Science Foundation. For more information on SESYNC and its activities, please visit http://www.sesync.org.


Press release from the SESYNC, University of Mariland.